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Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (3): 231-235,239.   DOI: 10.3969/j.issn.1004-616x.2023.03.014 Abstract （479）      PDF （1327KB）（948）       Knowledge map    Save Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (2): 148-153.   DOI: 10.3969/j.issn.1004-616x.2023.02.012 Abstract （727）      PDF （1101KB）（930）       Knowledge map    Save Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2022, 34 (4): 324-326.   DOI: 10.3969/j.issn.1004-616x.2022.04.014 Abstract （231）      PDF （876KB）（924）       Knowledge map    Save Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (4): 316-319.   DOI: 10.3969/j.issn.1004-616x.2023.04.013 Abstract （514）      PDF （847KB）（778）       Knowledge map    Save Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (2): 154-157,164.   DOI: 10.3969/j.issn.1004-616x.2023.02.013 Abstract （737）      PDF （1111KB）（777）       Knowledge map    Save Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2022, 34 (4): 314-317.   DOI: 10.3969/j.issn.1004-616x.2022.04.012 Abstract （248）      PDF （906KB）（775）       Knowledge map    Save Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (6): 485-488.   DOI: 10.3969/j.issn.1004-616x.2023.06.015 Abstract （206）      PDF （871KB）（756）       Knowledge map    Save Reference | Related Articles | Metrics

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Aging and malignant tumors—the neglected immunosenescence ZHANG Kaitai Carcinogenesis, Teratogenesis & Mutagenesis    2024, 36 (3): 169-171.   DOI: 10.3969/j.issn.1004-616x.2024.03.001 Abstract （376）      PDF （841KB）（720）       Knowledge map    Save Immunosenescence is an inherent and crucial aspect of the aging process. Malignant tumors which often develop among senior individuals are associated with immunosenescence. Besides the immune system's intrinsic aging，cancerous cells can exacerbate immunosenescence. This combination can lead to a reduction of young immune cells and an increase of older immune cells. Consequently，the immune system would have reduced ability to combat tumors. Interrupting the reciprocal interaction between malignant tumors and immunosenescence，as well as reversing the effects of immunosenescence，can hold promise for enhancing antitumor responses and improving long-term survival of cancer patients. Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2024, 36 (3): 248-252.   DOI: 10.3969/j.issn.1004-616x.2024.03.013 Abstract （592）      PDF （832KB）（645）       Knowledge map    Save Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2024, 36 (4): 320-324.   DOI: 10.3969/j.issn.1004-616x.2024.04.013 Abstract （555）      PDF （881KB）（640）       Knowledge map    Save Reference | Related Articles | Metrics

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Usefulness for combined detection of serum miRNA-183 and carbohydrate antigen 199 in the diagnosis and prognosis of gastric cancer HE Guangsi, WEI Jie, ZHANG Jian Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (6): 457-461,466.   DOI: 10.3969/j.issn.1004-616x.2023.06.009 Abstract （313）      PDF （1141KB）（636）       Knowledge map    Save OBJECTIVE：To investigate the usefulness for combined detection of serum miRNA-183 and carbohydrate antigen 199 (CA199) in the diagnosis and prognosis of gastric cancer. METHODS：From January 2017 to December 2021，fifty-two patients with gastric cancer，who were diagnosed in the Affiliated Chuzhou Hospital of Anhui Medical University were selected and their case data were used as the gastric cancer group. In addition，40 patients with benign stomach lesions were included as the non-gastric cancer group. Their levels of serum miRNA-183 and CA199 were determined. RESULTS：Differences in the levels of serum miRNA-183 between the gastric cancer and the non-gastric cancer groups were statistically significant (P<0.05). Expression levels of the serum miRNA-183 in patients with histopathologic classification of low-undifferentiated，T3-T4 and TNM stage III-IV were significantly higher than that in patients with histopathologic classification of medium-highly differentiated，T1-T2 and TNM stage I-II， (P<0.05). Expression levels of the serum CA199 in patients with histopathologic classification of low-undifferentiated and TNM stage III-IV were significantly higher than that in patients with histopathologic classification of medium-highly differentiated and TNM stage I-II， (P<0.05). Using the ROC curve analysis，the optimal cutoff value of the relative expression level of serum miRNA-183 was 4.11. The sensitivity and specificity were 67.31% and 80%，respectively. The area under the curve (AUC) was 0.771. The optimal cutoff value of the relative expression level of serum CA199 was 46.17 U/mL. The sensitivity and specificity were 53.8% and 87.5%，respectively. The area under the curve (AUC) was 0.724. The sensitivity and specificity of combined detection of serum miRNA-183 and CA199 in the diagnosis of gastric cancer were 76.92% and 87.5%，respectively，and the AUC was 0.882. The AUC of miRNA-183 combined with CA199 in diagnosis of gastric cancer was greater than that of miRNA-183 and CA199 independently. Kaplan-Meier analysis showed that the prognosis of patients with high expression of miRNA-183 was worse than that of patients with low expression，and the prognosis of patients with double high expression of miRNA-183 and CA199 was worse than that of patients without double high expression (P<0.05). CONCLUSION：There was a significant increase in the expression of miRNA-183 in serums of the patients with gastric cancer. Moreover，the expression levels of miRNA-183 were related to T stage，TNM stage and histological grading of tumor. Combined detection of serum miRNA-183 and CA199 improved the diagnostic efficiency of gastric cancer and predicted the prognosis of these patients. Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (6): 482-484,488.   DOI: 10.3969/j.issn.1004-616x.2023.06.014 Abstract （325）      PDF （940KB）（606）       Knowledge map    Save Reference | Related Articles | Metrics

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Pharmacokinetic study of nano-cationic liposomes loaded with siRNA in mice WEN Tianjiao, CHEN Xinran, BAI Jing, ZHENG Ying, WANG Yajuan, YU Peipei, CUI Jingxia Carcinogenesis, Teratogenesis & Mutagenesis    2022, 34 (6): 445-448,462.   DOI: 10.3969/j.issn.1004-616x.2022.06.007 Abstract （516）      PDF （1099KB）（578）       Knowledge map    Save OBJECTIVE:To investigate pharmacokinetics siRNA drugs in vivo and to analyze advantages of liposomes as drug carriers. METHODS:A previously constructed siRNA expression plasmid was loaded into nano-invisible cationic liposomes and used for investigations:bare siRNA plasmid group and siRNA plasmid liposomes group. DNase I digestion and serum stability were evaluated. Then,20 μg bare plasmid siRNA and liposome siRNA plasmid were injected into mice through their tail veins,and blood samples were collected at 0 min,5 min,15 min,30 min,1 h,2 h,4 h,12 h,and 24 h,respectively. Quantitative real-time PCR (qPCR) was used to quantitatively detect liposomes in mice,and the concentrations of siRNA plasmid at each time point was calculated. RESULTS:The bare plasmids were completely degraded in DNaseⅠwithin 20 min,and the degradation of plasmid liposomes was slow,with (20.16±2.47)% DNA remaining at 24 h. The bare plasmid only remained (11.03±0.92)% at 20 min in 80% serum,and was basically degraded at 1 h. The plasmid liposomes remained (10.26±1.04)% at 24 h in 80% serum. The stability of siRNA expression plasmid in DNaseⅠand serum was significantly improved by using liposomes as a carrier (P<0.05). The half-life of liposomal encapsulated plasmids in mice was about 2 h,while that of naked plasmids was only 6 min,and the difference was statistically significant (P<0.05). CONCLUSION:In vivo detection of siRNA liposomes can be accomplished by qPCR. Cationic liposomes can protect nucleic acid drugs inside the body,which is an efficient delivery carrier. At the same time,liposomes can improve stability of drugs in vivo and prolong the action time of drugs. Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2022, 34 (6): 481-484.   DOI: 10.3969/j.issn.1004-616x.2022.06.015 Abstract （282）      PDF （851KB）（576）       Knowledge map    Save Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (4): 310-315.   DOI: 10.3969/j.issn.1004-616x.2023.04.012 Abstract （494）      PDF （885KB）（575）       Knowledge map    Save Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2024, 36 (2): 159-163.   DOI: 10.3969/j.issn.1004-616x.2024.02.014 Abstract （194）      PDF （884KB）（566）       Knowledge map    Save Reference | Related Articles | Metrics

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Inhalation toxicity and safety of impurities CFC115 and HFC1243zf in the pharmaceutical HFA-134a ZHAO Yanjun, YANG Huiying, YI Zhongxun, SUN Huimin, LIN Fei Carcinogenesis, Teratogenesis & Mutagenesis    2022, 34 (4): 300-306.   DOI: 10.3969/j.issn.1004-616x.2022.04.010 Abstract （333）      PDF （1911KB）（563）       Knowledge map    Save OBJECTIVE: To evaluate inhalation toxicity and safety of impurities CFC115 and HFC1243zf in the pharmaceutical HFA-134a as propellant in pharmaceutical metered-dose inhalers. METHODS: Cytotoxicity assay, Reverse mutation assay, acute inhalation toxicity, 7-day repeat dose inhalation irritation study,21-day repeat dose inhalation toxicity study and active systemic anaphylaxis of the mixture of CFC115 and HFC1243zf (7:3,V/V) were tested to provide a basis for HFA 134a to control the impurity limit of CFC115 and HFC1243zf. RESULTS: Result from acute inhalation studies demonstrated that the 4-hour LC50 value was higher than 3 115 g/m3 for CFC115 and 832 g/m3 for HFC1243zf. Results from 7-day repeat dose inhalation irritation,active systemic anaphylaxis,Ames and cytotoxicity studies demonstrated that the mixture of CFC115 and HFC1243zf was not irritative, allergenic, mutagenic nor cytotoxic. 21-day repeat dose inhalation toxicity study were exposed, nose-only, to the mixture of CFC115 and HFC1243zf at levels of 3 205 g/m3 for CFC115 and 856 g/m3 for HFC1243zf 2 h/d,compared with the control group. Among these exposed rats,food intakes were decreased,body weight increased slowly. Values of Bas and Mon%,ALT, AST,ALP,T-BIL and UREA,and the urinary nitrite,ketone,PRO and LEU were mostly increased (P<0.05 or P<0.01). Brain coefficient values increased and ovarian wet weight values decreased. Histopathological changes of focal or multifocal endocardial necrosis and monocyte infiltration in 5 SD rats which had a treatment-related adverse effect. In addition,the lung wet weight and coefficient values of male rats decreased (P<0.01). CONCLUSION: In in vitro or short-term animal tests,the mixed gas of CFC115 and HFC1243zf showed no safety risk under high concentration of exposure or inhalation exposure. Long-term repeated high-concentration inhalation exposures showed a variety of toxic target organ effects in rats. However,these toxic concentrations were well above the clinical maximum exposure. Reference | Related Articles | Metrics

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Differential analysis of chromosomal aberrations among radiation workers in medical institutions ZHANG Zhongxin, ZHANG Ruifeng, LIU Xiaoming, MENG Qianqian, DANG Xuhong, ZHANG Jingyun, ZHAI Hongyan Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (3): 215-218.   DOI: 10.3969/j.issn.1004-616x.2023.03.010 Abstract （300）      PDF （896KB）（554）       Knowledge map    Save OBJECTIVE：To understand the impact of job type，gender，and employment duration on exposure doses of radiation workers in medical institutions，and to compare efficiency of chromosomal aberration analysis and thermoluminescence monitoring in assessing occupational health of the workers. METHODS：By using logistic regression analysis，the chromosomal aberration rates from different groups of radiation workers were analyzed based on three variables：job type，gender，and employment duration. The ROC curve was constructed based on individual dose monitoring results. RESULTS：Chromosome aberration rates of nuclear medicine workers were significantly higher than those who carried out X-ray imaging diagnosis (P<0.05)，while the rates for radiation therapy and interventional radiology workers were not statistically significant (P>0.05). There was no significant (P>0.05) impact from gender and employment duration on the chromosome aberration rates. The consistency between the chromosome aberration analysis and the abnormal rates of thermoluminescence monitoring (assuming that it exceeded 1 mSv as abnormal) was good. CONCLUSION：The radiation exposure doses of staff in the nuclear medicine department were significantly higher than that of staff in radiation diagnosis，radiotherapy and intervention. The evaluation criteria for the two means of occupational health monitoring (personal dose monitoring and chromosome aberration analysis) of radiation workers were inconsistent. Reference | Related Articles | Metrics

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Effects of blister agent nitrogen mustard exposure on the structure and function of mitochondria in hepatocytes WANG Zhao, LIU Sijia, LIU Jianhao, MA Chengfei, ZHAO Yushun, XU Anqi, AI Duo, QI Yujia, KONG Deqin, LIU Jiangzheng Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (2): 102-108,153.   DOI: 10.3969/j.issn.1004-616x.2023.02.004 Abstract （397）      PDF （3957KB）（539）       Knowledge map    Save OBJECTIVE： To investigate effects of the blister agent， nitrogen mustard (HN2)， on mitochondrial structure and function of hepatocytes，based on in vitro and in vivo models. METHODS：In the in vitro model，HepG2 cells were divided into normal control and HN2 exposure groups. The normal control group was treated with serum-free medium containing DMSO (0.1%) for 36 h，and the HN2 exposure group was treated with nitrogen mustard (8 μmol/L). After HN2 treatment for 36 h，cell viability was detected by CCK-8 method， mitochondrial membrane potential by JC-1 probe method， ATP content in cell homogenate and liver tissue by NADPH rate method， and mitochondrial function by Seahorse cell energy metabolism analyzer. Twenty C57BL/6 mice were divided into normal control group and HN2 exposure group. The HN2 exposure group was given a single intraperitoneal injection of nitrogen mustard hydrochloride (2 mg/kg)，and the normal control group was injected with normal saline. Serum and liver tissues were used to measure activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)， and pathological examination of liver tissues and electron microscope observations were performed. Contents of ATP and mitochondrial enzyme complexes I，II and III activities in liver tissues were determined by corresponding kits. RESULTS： In the in vitro model， compared with the normal control group， HN2 exposure decreased cell activity by about 16.2% (P<0.05)， the mitochondrial membrane potential by about 33.2% (P<0.05)， and mitochondrial energy metabolism was significantly abnormal. In the in vivo model，compared with the normal control group，HN2 exposure caused significant increased activities of serum ALT and AST. At the same time， there was large number of inflammatory cell infiltrations into liver tissues accompanied by liver parenchymal cell damage. Mitochondrial morphology was significantly abnormal： manifested as increased number，decreased size，loss or fragmentation of mitochondrial cristae，and significantly decreased activity of mitochondrial enzyme complexes I， II and III (P<0.05). CONCLUSION： HN2 exposure induced mitochondrial damage in hepatocytes and this may be one of the main toxic targets of HN2 poisoning. Results from our study provide new ideas for the prevention and treatment of acute liver injury induced by blister agents such as HN2. Reference | Related Articles | Metrics

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Protection against LPS-induced pro-inflammatory response by nuezhenide in macrophages JIANG Xiaoxu, SUN Muhan, ZHANG Boxu, WANG Yuyue, MA Jiajun, SHI Minjie, YU Weihua, GUO Xian Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (4): 245-252.   DOI: 10.3969/j.issn.1004-616x.2023.04.001 Abstract （362）      PDF （2353KB）（535）       Knowledge map    Save OBJECTIVE： This study aimed to investigate effects of nuezhenide (NED) on LPS-induced proinflammatory response in macrophages. METHODS： RAW264.7 cells were treated with 50 μmol/L NED for 12 hours. Differential gene expressions were detected via transcriptome，cell viability using the CCK8 kit，and apoptosis rates measured using Annexin V-FITC/PI staining，and expression and localization of Nrf2 protein were detected by immunofluorescence. The cells were treated with LPS (100 ng/mL) and NED (12.5，25 and 50 μmol/L) for 12 hours. Then，TNF-α and IL-6 contents in the supernatant of cultured cells were determined by ELISA，and expressions of TNF-α and IL-6 by RT-PCR. Moreover，ROS，mitochondrial mass，and membrane potential were measured by flow cytometry after staining with DCFH-DA，MitoTracker-Green and JC-1，respectively. Enzyme activities of SOD and CAT，activities of mitochondrial complexes I and Ⅲ，as well as ATP contents were determined using commercial kits. RESULTS： Our results show that 50 μmol/L NED had no significant effects on survival and apoptosis of the RAW264.7 macrophages (P>0.05). However，NED treatments blunted LPS-induced expression of TNF-α and IL-6 (P<0.05)，and enhanced expression of anti-inflammatory cytokines (P<0.05). Meanwhile，NED significantly promoteed Nrf2 nuclear translocation and downstream antioxidant transcription (P<0.05)，which contributed to inhibition of LPS-induced accumulation of ROS and GSSG (P<0.05). In addition，NED reversed the LPS-induced decreased of mitochondrial membrane potential，mitochondrial complexes I and III activities，as well as ATP contents through promoting mitochondrial biogenesis (P<0.05). CONCLUSION： NED inhibited LPS-induced macrophages pro-inflammatory differentiation through enhancing Nrf2 antioxidant system and mitochondrial biogenesis. Application of NED may be a potential strategy for treatment of inflammatory diseases. Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2024, 36 (1): 66-69,76.   DOI: 10.3969/j.issn.1004-616x.2024.01.011 Abstract （282）      PDF （1035KB）（534）       Knowledge map    Save Reference | Related Articles | Metrics

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Sub-chronic toxicity of polyphenol and polysaccharid extracts from Areca catechu in Wistar rats LI Min, HE Ning, ZHANG Dalong, GUAN Tong, QIAN Zhiyong Carcinogenesis, Teratogenesis & Mutagenesis    2022, 34 (4): 307-313,317.   DOI: 10.3969/j.issn.1004-616x.2022.04.011 Abstract （357）      PDF （3617KB）（527）       Knowledge map    Save OBJECTIVE: To investigate sub-chronic toxicity of polyphenol and polysaccharide extracts from Areca catechu in Wistar rats. METHODS: A total of 100 Wistar rats were randomly divided into control group,and Areca polysaccharide polyphenols-treated groups:0.28,0.83 and 2.5 g/kg. From the 0.28 and 0.83 g/kg groups,20 in each group,were killed after 90 days of exposure. From the 2.50 g/kg and control groups (30 in each group),20 were killed after 90 days of exposure,and treatments were stopped for the remaining 10 which received normal feeding for the subsequent 28 days. Each treated rat received 10 mL/kg volume of continuous intragastric administration for 90 days,once a day,and the control rats received equal volume of distilled water. Changes of body weight, food availability, hematology, biochemical parameters, urinalysis, main organ coefficient and histopathological examination were detected. RESULTS: Total weight gain of the 2.50 g/kg group was lower than that of the control group during the treatment period. There were no significant differences in the food utilization rates between groups except that the male rats in the first week of 2.50 g/kg group was lower than that in the control group. Five male and five female rats in the 2.50 g/kg group showed symptoms of poor spirit,rough coat and sluggish reaction after 3 weeks of treatment. Two male and two female rats died during the treatment period. Flatulence and thinning of gastrointestinal wall were observed in naked rats,but no obvious abnormalities were found in the histopathological examination of major organs. There were no obvious abnormalities in other dose groups compared with the control group during the exposure and the recovery periods. Although there were statistical differences in hematology,blood biochemistry and individual urine indexes between the control and the other dose groups,they were all within the range of normal test values in our laboratory, and had no biological significance. The organ coefficient and histopathological examination of the main organs showed no obvious abnormalities. It was considered that the death of rats might have been caused by gastrointestinal flatulence due to intestinal fermentation of a large amount of polysaccharide. Under the conditions of this study,90-day oral treatment with 0.83 g/kg areca polysaccharide polyphenols was considered to be at the no observed adverse effect level (NOAEL). CONCLUSION: Oral administration of 2.50 g/kg areca polysaccharides polyphenols for 90 days caused lethargy and flatulence in Wistar rats. Although this symptom was reversible,excessive dosage caused mortality. Therefore,development and utilization of areca polysaccharides polyphenols should be controlled within the safe dose range. Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2024, 36 (2): 164-167.   DOI: 10.3969/j.issn.1004-616x.2024.02.015 Abstract （182）      PDF （931KB）（516）       Knowledge map    Save Reference | Related Articles | Metrics

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Genotoxicity evaluation of electronic cigarette liquid using the in vitro mammalian cell micronucleus test DU Xiuming, ZHANG Liting, XU Lingzhi Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (4): 302-305.   DOI: 10.3969/j.issn.1004-616x.2023.04.010 Abstract （328）      PDF （936KB）（510）       Knowledge map    Save OBJECTIVE： According to the OECD 487 Guidelines for testing of chemicals，the in vitro mammalian cell micronucleus test was used to determine whether the electronic cigarette liquid was mutagenic or not. METHODS： The doses for the liquid were 1.25，2.50 and 5.00 μL/mL. Solvent and positive controls were included，and replicate cultures were set up per dose in the test. The CHL cells were exposed to the liquid in the presence or absence of an exogenous metabolic activation system (S9)，for 4 and 24 hours of incubation. Then，they were harvested，exposed to hypotonic solution and fixed. The cells were then stained with acridine orange and observed under fluorescence microscopy. For each dose group，2 000 binucleated cells were selected for micronucleus rate analysis. RESULTS： After incubation for 4 hours with the dose levels of 1.25，2.50 and 5.00 μL/mL，the induced micronucleus rates without S9 (4 h，-S9)were 2.50‰，1.50‰ and 1.50‰ respectively；and 1.50‰，2.00‰ and 1.00‰ respectively with S9 (4 h，+S9). After 24 hours treatment without S9 (24 h，-S9)，the rates were 1.50‰，1.00‰ and 1.00‰，respectively.. Compared with the solvent control group，there was no statistically significant difference observed (P>0.05). CONCLUSION： Under the current test conditions，electronic cigarette liquid showed no evidence of mutagenic potential in the CHL at the tested dose level of 1.25-5 mg/mL. Reference | Related Articles | Metrics

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Acute and sub-chronic toxicity of tris(1, 3-dichloroisopropyl) phosphate in rats ZHANG Jiuhong, CHEN Xiao, ZHAO Jing, XU Benhong, WU Desheng, LIU Jianjun Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (6): 431-438.   DOI: 10.3969/j.issn.1004-616x.2023.06.005 Abstract （314）      PDF （11857KB）（510）       Knowledge map    Save OBJECTIVE：To investigate the acute and sub-chronic toxicity of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) in rats. METHODS：In the acute toxicity test，50 SD rats at SPF level were randomly divided into 5 groups，with 10 rats per group，equally male and female，and given a single oral dose of 464，1 000，2 150，4 640，and 10 000 mg/kg. In the sub-chronic toxicity test，80 SD rats at the SPF level were randomly divided into 4 groups of 20 rats per group，equally divided between males and females，and orally administered a dose of 0，13.3，40，and 120 (high dose) mg/kg per day for 112 consecutive days. Organs were harvested and weighed，and the organ coefficient was calculated. Blood routine and blood biochemical indices were examined. HE staining was performed to analyze histopathological changes. Representative indicators were selected for toxic effects using the baseline dose BMD method to assess exposure levels at specific risk levels，compared with the NOAEL method reference values to analyze relatively more specific and sensitive dose limits. RESULTS：The LD50 of TDCIPP in acute oral toxicity test in SD rats was 2 000-2 300 mg/kg. Compared with the control group，the 120 mg/(kg·d) sub-chronic exposure dose significantly affected the body mass growth of female rats；the organ coefficients of the liver and kidney of rats in the 40 and 120 mg/(kg·d) dose of TDCIPP group were significantly elevated (P<0.05)；and the leukocyte counts，lymphocyte counts，and monocyte counts of male rats in the 40 mg/(kg·d) dose of TDCIPP group were significantly elevated (P<0.05). The mean values of white blood cell count，lymphocyte count，monocyte count and eosinophil count in male rats dosed with 40 mg/(kg·d) were significantly higher than those in the control group (P<0.05). The mean values of AST in male rats were significantly lower than those in the control group in the 40 mg/(kg·d) dose group；the mean values of ALT and AST in female rats in the 40 mg/(kg·d) dose group were significantly lower than those in the control group (P<0.05)；and HE staining of the 40 and 120 mg/(kg·d) dose groups showed significant renal pathology damage. The highest NOAEL of 13.3 mg/(kg·d) was assessed based on the no-observed-adverse-effects level (NOAEL). The benchmark dose method (BMD)，which uses blood creatinine as an indicator of renal function，determined the reference dose in the risk assessment with a limit of 2.696 mg/(kg·d). CONCLUSION：The livers and kidneys were the main target organs of TDCIPP in rats. Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (3): 240-244.   DOI: 10.3969/j.issn.1004-616x.2023.03.016 Abstract （290）      PDF （849KB）（507）       Knowledge map    Save Reference | Related Articles | Metrics

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ALDH3A1 activates GMA-induced malignant transformation of epithelial mesenchymal transition in 16HBE cells via the IL-6/STAT3 signalling pathway WANG Quankai, JIN Huiping, LI Xinwei, CUI Xufang, GU Yiting, WUHAN Baolier, KANG Tongying, XU Jianning Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (6): 405-411.   DOI: 10.3969/j.issn.1004-616x.2023.06.001 Abstract （348）      PDF （1718KB）（504）       Knowledge map    Save OBJECTIVE：As a carcinogen classified as Group 2A by the International Agency for Research on Cancer (IARC)，glycidyl methacrylate (GMA) is widely used in the synthesis and modification of various composite materials. However，the specific carcinogenic mechanism of GMA remains unclear. This study aimed to investigate whether the key molecular mechanisms underlying the malignant transformation of 16HBE cells induced by GMA are associated with the expression of aldehyde dehydrogenase 3A1 (ALDH3A1). METHODS：The transient transfection technique was used to overexpress ALDH3A1 in the GMA-induced malignant transformed 16HBE cells，which was established by our research group in previous work. qPCR and Western blot techniques were used to analyze the gene and protein expression levels of IL-6/signal transducer and activator of transcription 3 (STAT3) pathway and epithelial-mesenchymal transition (EMT) markers，including E-cadherin，Vimentin，matrix metalloproteinase 3 (MMP3) and Snail protein and mRNA expression. RESULTS：The qPCR and Western blot results showed that，compared to the control group，the ALDH3A1 overexpression group upregulation of E-cadherin expression，and downregulation of IL-6，STAT3，p-STAT3，MMP3 and Snail expression (P<0.05). Additionally，the transcription levels of MMP3，Snail，and Vimentin were downregulated (P<0.05). The results indicated that ALDH3A1 reduced the expression of several key proteins involved in the EMT process in GMA-induced malignant transformed 16HBE cells by inhibiting the activation of the IL6/STAT3 pathway. CONCLUSION：ALDH3A1 is closely associated with the GMA-induced malignant transformation process in 16HBE cells，and it inhibits the activation of the IL-6/STAT3 pathway，thereby attenuating the expression of multiple key proteins involved in the EMT process. These findings contribute to elucidating the carcinogenic mechanism of GMA and provide potential biomarkers for the assessment of health effects of GMA exposure. Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (3): 224-227.   DOI: 10.3969/j.issn.1004-616x.2023.03.012 Abstract （189）      PDF （831KB）（499）       Knowledge map    Save Reference | Related Articles | Metrics

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Screening of plasma exosome microRNAs in patients with lung cancer LIU Xia, GAO Zibo, DING Lihua, WU Yongjun Carcinogenesis, Teratogenesis & Mutagenesis    2022, 34 (6): 407-412.   DOI: 10.3969/j.issn.1004-616x.2022.06.001 Abstract （471）      PDF （2481KB）（488）       Knowledge map    Save OBJECTIVE:Existence of miRNAs in plasma exosomes of lung cancer patients were screened to develop new methods for the screening and auxiliary diagnosis of lung cancers. METHODS:Plasma samples were collected from 6 lung cancer patients (3 adenocarcinomas,2 squamous carcinomas and 1 small cell lung cancer) and 4 healthy controls. Agilent Bioanalyzer was used for qualitative inspection of the extracted RNA. Plasma exosomal miRNA was analyzed by high-throughput sequencing. Target gene prediction was performed by TargetScan,PITA and miRNAorg database,and R software was applied for KEGG and GO analysis of target genes. RESULTS:The exosomal differential miRNA expression analyses showed that 142 miRNAs were expressed abnormally in the lung cancer group compared with to the normal group,with 62 miRNAs up-regulated and 80 miRNAs down-regulated. GO analysis showed that these abnormally-expressed (target) genes were mainly involved in DNA-based template transcription,transcriptional regulation and signal transduction,etc. The target KEGG analysis indicated that these target genes were mainly involved in axon guidance signaling pathway,calcium signaling pathway,and actin cytoskeleton regulation. CONCLUSION:Our data suggest that differentially expressed miRNAs may have good predictive potential for lung cancer metastasis. In addition,they may be candidate biomarkers for the screening and diagnosis of lung cancers. Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (2): 144-147.   DOI: 10.3969/j.issn.1004-616x.2023.02.011 Abstract （218）      PDF （906KB）（475）       Knowledge map    Save Reference | Related Articles | Metrics

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Occurrence of the TMPRSS2::ETS fusion gene in Chinese patients with prostate cancer: a meta-analysis ZHANG Jiawei, YUAN Qin, XU Xianrong, FANG Xuexian, CAO Yifei, YANG Jun Carcinogenesis, Teratogenesis & Mutagenesis    2022, 34 (5): 344-352.   DOI: 10.3969/j.issn.1004-616x.2022.05.003 Abstract （449）      PDF （1846KB）（473）       Knowledge map    Save OBJECTIVE: To use meta-analysis for assessing the occurrence of TMPRSS2::ERG fusion gene in Chinese patients with prostate cancer.METHODS: A systematic search was conducted through PubMed,Web of Science,Google Scholar,China knowledge Resource Database (CNKI),Wanfang Medical online Database and VIP Database.The risk of bias was assessed using QUADAS-2 and a meta-analysis was performed using Stata12.0 and Review Manager 5.3 to evaluate the occurrence of TMPRSS2::ERG fusion gene in Chinese prostate cancer patients.RESULTS: A total of 16 articles were included.The incidence rate of TMPRSS2::ERG fusion gene in prostate cancer was 16.7%[95% CI (14.5%,18.8%)].Regarding the type of samples,biopsy specimens showed the incidence rate of fusion gene was 17.9%[95% CI (15.8%,20.1%)].When using immunohistochemistry (IHC) detection technology,the incidence rate of fusion gene was 16.6%[95% CI (13.0%,20.2%)].CONCLUSION: The occurrence of TMPRSS2::ERG fusion gene was low in Chinese prostate cancer patients,therefore,the TMPRSS2::ERG fusion gene cannot be used as a diagnostic marker for Chinese prostate cancer patients. Reference | Related Articles | Metrics

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Application of an in vivo alkaline comet assay in genotoxicity of two polyether ether ketone materials SUN Lingxiao, LIU Xiangdong, LIU Zengxiang, WANG Luanluan, ZHU Fuyu, SUN Xiaoxia, LIU Chenghu Carcinogenesis, Teratogenesis & Mutagenesis    2022, 34 (5): 388-394,399.   DOI: 10.3969/j.issn.1004-616x.2022.05.010 Abstract （372）      PDF （3790KB）（461）       Knowledge map    Save OBJECTIVE: An in vivo mammalian alkaline comet test was used to detect genotoxicity of two kinds of polyether ether ketone materials,and to develop the method for genotoxicity evaluation of medical devices.METHODS: Two polyether ether ketone materials were extracted with 0.9% sodium chloride injection (SC) and cottonseed oil (CSO) into rats,and used as the test solution.SC and CSO were prepared the same way and served as the negative controls.Methyl methanesulfonate (MMS) was used as positive control.70 SD rats (half males and half females) received two treatments at 24 h intervals.The SC and MMS groups of rats received treatments through intravenous injection at a dose of 10 mL/kg.The CSO group received treatments through intraperitoneal injection at a dose of 5 mL/kg.All rats were sacrificed at 3 h after the last treatments.Their livers and kidneys were weighed and histopathological examined.Single-cell suspensions were prepared from liver,kidney and peripheral blood for the alkaline comet assay which determined DNA damage via% tail DNA,tail moments and Olive tail moments.RESULTS: Under the conditions of this study,the liver and kidney coefficients of the test solution and the MMS positive control group showed no statistically significant differences compared with the SC and CSO negative control groups,respectively.The shape and structure of the liver and kidney of all rats were normal without obvious histopathological changes.There were statistically significant differences in the% tail DNA,tail moment and Olive tail moment in the MMS positive control group (P<0.01) and there were no statistically significant differences in the two polyether ether ketone materials groups (P>0.05) compared with the SC and CSO negative control groups.CONCLUSION: The method of in vivo alkaline comet assay for genotoxicity of medical devices was successfully tested.The two polyether ether ketone materials were considered unable to induce DNA strand breakage in the rat liver under the conditions of this study. Reference | Related Articles | Metrics

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Integrative lncRNA-mRNA co-expression network analysis in the chronic cadmium-exposed esophageal squamous cell carcinoma cell PENG Lin, ZENG Mingqin, CHEN Jiongyu, ZHANG Xiarong, ZHU Rui, HUANG Yiteng Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (4): 266-272,278.   DOI: 10.3969/j.issn.1004-616x.2023.04.004 Abstract （314）      PDF （3299KB）（456）       Knowledge map    Save OBJECTIVE： To investigate involvement of the long non-coding RNA (lncRNA) and messenger RNA (mRNA) co-expression network in chronic low-dose cadmium exposure in esophageal squamous carcinoma (ESCC) cells，and to explore molecular mechanisms of hub lncRNAs and mRNAs in the cadmium-associated cancer progression and chemo-and radio-resistance. METHODS： EC109 cells were continually treated with 5 μmol/L cadmium chloride over 12 weeks to construct the chronic cadmium treated (CCT)-ESCC cell model，named as CCT-EC109. The whole-transcriptome sequencing was performed by the Illumina NovaSeq 6000 system，and then bioinformatics methods were applied to identify the differentially expressed (DE)- lncRNA and DE-mRNA expression profiles. Functions of target genes of DE-lncRNA were then predicted based on gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) forecast analysis. The lncRNA-mRNA co-expression network was conducted based on the Pearson correlation coefficient and the screened lncRNAs and mRNAs were verified using quantitative real-time polymerase chain reaction (qPCR). RESULTS： A total of 2 794 DE-lncRNAs and 4 267 DE-mRNAs were identified in the EC109 and CCT-EC109 cells. Intersection of the target genes of DE-lncRNA and DE-mRNAs yielded 1 546 cadmium-related mRNAs targeted by corresponding DE-lncRNA. GO analysis showed these genes were mainly enriched in metabolic process，membrane components and membrane closed cavity，and catalytic reaction，etc. For KEGG analysis，Hippo was shown to be the most significant enrichment pathway. Thirty-eight mRNAs were identified to be co-expressed with the top ten DE-lncRNAs. The results of qPCR assay indicated that both the key lncRNA NONHSAT097388.2 and its co-expressed mRNAs including EMP2，ECE1，ORAI1，and ZNF713，were significantly downregulated in the exposed cell line (all P<0.01)，while the expressions of PGF and MFAP5 were found to be upregulated (both of P<0.05). CONCLUSION： LncRNA-mRNA co-expression networks may play important roles in the mechanisms of progression and resistance in ESCC cells chronically exposed to cadmium. Meanwhile，these hub RNAs may serve as prognostic biomarkers or therapeutic targets for the ESCC patients with cadmium exposure. Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (4): 320-324.   DOI: 10.3969/j.issn.1004-616x.2023.04.014 Abstract （296）      PDF （975KB）（450）       Knowledge map    Save Reference | Related Articles | Metrics

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Relationships between DNA ploidy abnormality and EGFR mutation in pleural effusions, and their effects on prognosis of lung adenocarcinomas LIU Ying, WANG Rui, GUO Xiao, DONG Lüli, ZHANG Yan, ZHAO Yinhuan, DU Yun Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (3): 178-182,186.   DOI: 10.3969/j.issn.1004-616x.2023.03.003 Abstract （354）      PDF （994KB）（437）       Knowledge map    Save OBJECTIVE：Relationships between DNA ploidy abnormality and epidermal growth factor receptor (EGFR) gene mutation in pleural effusion from metastatic lung adenocarcinomas and their effects on prognosis of patients. METHODS：Clinical data of 439 patients with lung adenocarcinomas and with malignant pleural effusions were collected from the Fourth Hospital of Hebei Medical University from 2012 to 2019. DNA content in cells from pleural effusions was detected by computer aided DNA ploidy quantitative analysis. Percentages of cells with greater than 5c，the number of cells with greater than 9c，the maximum DNA index (DI) value，the average DI value of cells with greater than 5c and the peak of aneuploid cells were calculated. Differences of DNA ploidy and EGFR gene mutation among groups were compared，and correlations between DNA ploidy and EGFR mutation were tested to analyze the values of DNA ploidy and EGFR gene mutation in prognosis of lung adenocarcinoma. RESULTS：EGFR mutations were detected in 244 (55.58%) of 439 patients. The mutation rate was significantly reduced in male patients，and in patients with a history of smoking，compared to the controls (P<0.05). In addition，the percentage of cells greater than 5c <14%，the number of cells greater than 9c <8，the maximum DI value <6，and the mean value of cells greater than 5c <5 (P<0.05). The mutation rate of EGFR gene was different with different aneuploid cell peak，and compared with the nonpeak group，the mutation rate of EGFR gene was higher with single and double peak (P<0.05)，while there was no significant difference in EGFR mutation rate between multi-peak and other groups. Compared with the EGFR wild-type patients，EGFR mutant patients had a higher mean rank in the percentage of cells greater than 5c，the number of cells greater than 9c，the maximum DI，the mean DI of cells greater than 5c，and the aneuploid cell peak number，and all five indexes were weakly positively correlated with EGFR mutation. Univariate survival analysis showed that the median overall survival time of patients with greater than 5c cell percentage ≥14%，greater than 9C cell number ≥8 and EGFR mutation were longer than that of the controls. Multivariate survival analysis showed that DNA ploidy was not associated with patient prognosis，and EGFR gene mutation was an independent prognostic factor in patients with advanced lung adenocarcinoma. CONCLUSION：There was a positive correlation between EGFR gene mutation and DNA ploidy abnormality in patients with advanced lung adenocarcinoma，and DNA ploidy abnormality was a potential predictor of EGFR gene mutation. DNA ploidy was not an independent prognostic factor in patients with advanced lung adenocarcinoma. Patients with EGFR gene mutation had a better prognosis than the wild-type patients. Reference | Related Articles | Metrics

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Carcinogenesis, Teratogenesis & Mutagenesis    2022, 34 (5): 404-407.   DOI: 10.3969/j.issn.1004-616x.2022.05.013 Abstract （365）      PDF （881KB）（435）       Knowledge map    Save Reference | Related Articles | Metrics

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Effect of glycyrrhizic acid on human lung adenocarcinoma cells and its mechanism HUANG Ji, LI Zixuan, XU Jiaqi, LUO Xiu, SUN Zhenxiao Carcinogenesis, Teratogenesis & Mutagenesis    2025, 37 (1): 56-62.   DOI: 10.3969/j.issn.1004-616x.2025.01.010 Abstract （162）      PDF （2749KB）（435）       Knowledge map    Save OBJECTIVE： To explore whether glycyrrhizic acid has an anti-lung adenocarcinoma effect and its mechanism in vitro. METHODS： Human lung adenocarcinoma cells A549，NCI-H1299，normal human lung epithelial cells Beas-2b，and human umbilical vein endothelial cells (HUVECs) were treated with glycyrrhizic acid at concentrations of 0.5-6 mmol/L for 48 hours. The MTT assay was used to detect effects on growth and viability. Flow cytometry was used to assess effects on cell cycle and apoptosis in A549 cells，comparing the untreated with cells treated with 4 mmol/L glycyrrhizic acid. Network pharmacology was employed to predict key targets and pathways impacted by glycyrrhizic acid. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to verify key targets after treatment with 4 mmol/L glycyrrhizic acid in A549 cells. RESULTS： At concentrations of 1-6 mmol/L，glycyrrhizic acid significantly inhibited the viability of A549 and NCI-H1299 cells，while showing a weaker inhibitory effect on normal lung epithelial cells Beas-2b and HUVECs. After treatment with 4 mmol/L glycyrrhizic acid，the proportion of apoptotic cells in the control group was (3.73±1.43)%，compared to (44.41±10.28)% in the treatment group. The proportion of cells in the G0/G1 phase in the control group was (45.7±0.98)%，while the treatment group had (53.03±2.25)%. Network pharmacology predicted the key targets were caspase 3，STAT3，SRC，MMP9，and PTGS2，which are involved in apoptosis，cell cycle arrest，and oxidative stress signaling pathways. In addition，glycyrrhizic acid significantly reduced the mRNA expression of SRC and PTGS2 in A549 cells，inhibited the expression of p-STAT3，and activated the cleavage of caspase 3. CONCLUSION： Our in vitro studies indicate that glycyrrhizic acid selectively killed human lung adenocarcinoma cells A549，primarily through the induction of cell cycle arrest and apoptosis，possibly involving downregulation of SRC，PTGS2，and p-STAT3 expression levels and activation of caspase 3. Reference | Related Articles | Metrics

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Correlation and prognostic value of serum miR-146a with TNF-α and Treg in patients with non-small cell lung cancer XU Jinhua, LI Jingjing, WU Guofeng, REN Yajun, WANG Xue, ZHANG Qianyun Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (6): 462-466.   DOI: 10.3969/j.issn.1004-616x.2023.06.010 Abstract （249）      PDF （1115KB）（432）       Knowledge map    Save OBJECTIVE：To investigate correlations of serum miR-146a with tumor necrosis factor α (TNF-α) and T-regulatory cells (Treg) in patients with non-small cell lung cancer (NSCLC) and prognostic valuesa in the patients. METHODS：From June 2020 to November 2021，a total of 162 patients with advanced NSCLC who were treated in Cangzhou Central Hospital were selected for our study. Levels of miR-146a in patients were detected using fluorescence quantitative PCR ELISA，serum levels of miR-146a and TNF-α were detected using enzyme-linked immunoassay，and Treg levels were detected using flow cytometry. Pearson correlation was used to analyze correlations among miR-146a expressions， TNF-α concentrations and Treg proportion. Multi-factor logistic regression was used to analyze whether the relative expression levels of miR-146a was a prognostic risk factor for the patients. ROC curve was used to compare the predictive efficacy of miR-146a on prognosis. RESULTS：The relative expression levels of miR-146a was positively correlated with the concentrations of TNF-α (r=0.651，P<0.01)，and negatively correlated with the proportions of Treg (r=-0.676，P<0.01). The relative expression levels of miR-146a and the concentrations of TNF-α were prognostic risk factors (OR=1.95 and 1.39，respectively；P<0.01). Treg was a prognostic protective factor for death in NSCLC patients (OR=0.53；P<0.01). The AUC of miR-146a was 0.959 and 95%CI (0.934，0.985)，P<0.01. CONCLUSION：Serum miR-146a in NSCLC patients was positively correlated with TNF-α and negatively correlated with Treg，which was shown to be a risk factor for death in NSCLC patients and to have high prognostic value for NSCLC. Reference | Related Articles | Metrics

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Clinical value in using droplet digital PCR to detect urinary cfDNA FGFR3 S249C mutation in patients with urothelial carcinoma ZULIHUMAER Aizimuaji, ZHAO Huan, MA Sheng, GAO Ran, WANG Yaru, XIAO Ting Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (3): 165-171.   DOI: 10.3969/j.issn.1004-616x.2023.03.001 Abstract （375）      PDF （1493KB）（430）       Knowledge map    Save OBJECTIVE：The purpose of this study was to improve diagnostic efficacy of urothelial carcinoma (UC) by using the droplet digital PCR (ddPCR) to detect FGFR3 S249C (fibroblast growth factor receptor 3，FGFR3)mutation in cfDNAs which were extracted from urine of UC patients and in combination with urinary cytology. METHODS：Urine samples were collected from 27 UC patients and DNA samples were extracted. The FGFR3 S249C mutation in urinary cfDNA was detected by ddPCR. Receiver operating characteristic curves (ROC) were applied to evaluate the diagnostic efficacy of urinary cfDNA for patients with unclear urinary cytology but a clear pathological diagnosis of UC. RESULTS：The detection rate of the FGFR3 S249C mutation for UC was 25.9% (7/27). The detection rate of the mutation classified by TPS (The Paris system for reporting urinary cytology) was 18.8% (3/16) in HGUC (high-grade urothelial carcinoma)，50% (4/8) in SHGUC (suspicious for high-grade urothelial carcinoma)，and 0 (0/3) in NHGUC (negative for high-grade urothelial carcinoma). The mutation rate was 25.0% (1/4) in non-invasive UC and 31.6%(6/19)in invasive UC. The detection rate of positive mutation by ddPCR in SHGUC was 50.0% (4/8)，and the area under the ROC for the diagnosis of UC by the mutation was 0.781 with 95% CI (0.407，1.000)，which showed good accuracy for its diagnosis. CONCLUSION：Measurement of the FGFR3 S249C mutation in urinary cfDNA using ddPCR as a non-invasive assay could improve the diagnostic efficacy for UC with unclear urinary cytology diagnosis. Reference | Related Articles | Metrics

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Bioinformatic analysis of immune cell infiltration and tumor mutation burden in colorectal cancer WANG Na, WANG Ping, HE Yijia, ZENG Jing, HAN Congling, WANG Sirui, XUAN Xiaoyan Carcinogenesis, Teratogenesis & Mutagenesis    2023, 35 (3): 172-177.   DOI: 10.3969/j.issn.1004-616x.2023.03.002 Abstract （351）      PDF （7951KB）（426）       Knowledge map    Save OBJECTIVE：Expression of immune cell infiltration (ICI) and tumor mutation burden (TMB) in colorectal cancer (CRC) samples were analyzed using bioinformatic analysis. METHODS：The CIBERSORT and ESTIMATE algorithms were used to calculate relative fractions of immune cells in CRC samples，and the Spearman test was used to analyze correlations among infiltrating immune cells. The ConsensusClusterPlus was used to cluster the CRC samples into ICI cluster A and ICI cluster B based on similarity of the relative fractions of immune cell infiltration. The overall survival (OS) of patients were analyzed by Kaplan-Meier. The ICI score model of CRC samples was constructed based on the signature gene A and signature gene B，and ICI scores of each CRC samples were calculated. CRC patients were divided into two groups based on the ICI scores：ICI score High and Low. The OS of patients were analyzed by Kaplan-Meier，and GSEA was used to analyze the enrichment pathways in each group. TMB was calculated and presented by maftool. Based on the TMB，the CRC patients were divided into H-TMB and L-TMB. The OS of patients between two groups were analyzed by Kaplan-Meier. RESULTS：There was no statistical difference in OS between patients in ICI clusters A and B. However，patients in the ICI score high group had longer OS than those in the ICI score low group. Gene sets which were closely related to intestinal physiological functions were enriched in the ICI score high samples，while gene sets which were closely related to tumor formation，development and metastasis were enriched in the ICI score low group. There was no significant difference in TMB between ICI score low and ICI score high samples. The frequencies of KRAS，TP53 and APC were the highest compared with that of other genes in both the ICI score low and high groups. The patients in the L-TMB group had longer OS than those in the H-TMB group. CONCLUSION：CRC patients in the ICI score high group had longer OS than those in the ICI score low group，and patienets in the L-TMB group had longer OS than those in the H-TMB group. Reference | Related Articles | Metrics