血清miRNA-183与CA199联合检测在胃癌诊断和预后评估中的价值

doi:10.3969/j.issn.1004-616x.2023.06.009

摘要/Abstract

摘要： 目的：探讨血清miRNA-183与糖类抗原199(CA199)联合检测在胃癌诊断和预后评估中的价值。方法：选取2017年1月—2021年12月在安徽医科大学附属滁州医院确诊的52例胃癌患者，将其病例资料纳入胃癌组，另选同期诊断为胃部良性病变的40例患者纳入对照组。采集其外周静脉血，分别采用逆转录实时荧光定量PCR(RT-qPCR)和化学发光免疫法检测血清miRNA-183、CA199水平，比较胃癌患者与对照组间的差异，绘制受试者工作特征曲线(ROC)，分析以上指标单独及联合检测在胃癌诊断中的价值。分析血清miRNA-183和CA199水平与胃癌患者临床病理指标的关系，采用Kaplan-Meier生存曲线分析血清miRNA-183和CA199水平对胃癌患者预后的影响。结果：与对照组相比，胃癌组患者血清中miRNA-183表达水平明显升高，差异具有统计学意义(P<0.05)。组织病理分型为低-未分化、T3~T4以及TNM分期为III~IV期胃癌患者血清miRNA-183的表达水平较组织病理分型为中-高分化、T1~T2和TNM分期为I~II期的胃癌患者明显升高(P<0.05)；组织病理分型为低-未分化、TNM分期为III-IV期胃癌患者血清CA199的表达水平较组织病理分型为中-高分化、TNM分期为I-II期的胃癌患者亦明显升高(P<0.05)。采用ROC曲线分析得出miRNA-183相对表达量4.11为诊断胃癌的最佳临界值，灵敏度与特异度分别为67.31%和80%，ROC曲线下面积(AUC)为0.771；CA199以46.17 U/mL为诊断胃癌的最佳临界值，敏感度与特异度分别为53.8%和87.5%，AUC为0.724；联合检测血清miRNA-183与CA199诊断胃癌对应的敏感度及特异度分别为76.92%和87.5%，AUC为0.882。miRNA-183联合CA199诊断胃癌的AUC大于miRNA-183或CA199独立诊断，差异均具有统计学意义(P<0.05)。Kaplan-Meier分析显示，miRNA-183高表达水平组患者的预后较miRNA-183低水平组患者差，miRNA-183和CA199均高表达患者预后更差(P<0.05)。结论：胃癌患者血清miRNA-183表达明显升高，且与肿瘤的T分期、TNM分期、组织学分级相关；血清miRNA-183与CA199联合检测可以提高胃癌诊断效能，预测胃癌患者的预后。

关键词: miRNA-183, CA199, 胃癌, 肿瘤标记物

Abstract: 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.

Key words: miRNA-183, carbohydrate antigen 199, gastric cancer, tumor markets

中图分类号:

R735.2

何广思, 魏洁, 张健. 血清miRNA-183与CA199联合检测在胃癌诊断和预后评估中的价值[J]. 癌变·畸变·突变, 2023, 35(6): 457-461,466.

HE Guangsi, WEI Jie, ZHANG Jian. Usefulness for combined detection of serum miRNA-183 and carbohydrate antigen 199 in the diagnosis and prognosis of gastric cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(6): 457-461,466.

参考文献

[1] CHEN W Q, ZHENG R S, BAADE P D, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132.
[2] 陈洛海, 张雨, 陈旻湖, 等. 肿瘤标志物癌胚抗原、甲胎蛋白、糖类抗原125和糖类抗原19-9在胃肠胰神经内分泌肿瘤中的升高情况及其对预后评估的价值[J]. 中华胃肠外科杂志, 2017, 20(9):1002-1008.
[3] 钟兰, 刘梦琼, 吴华, 等. 胃癌患者血清CA125、CA724、CEA、CA199水平的表达及与临床病理特征的关系研究[J]. 现代生物医学进展, 2018, 18(18):3550-3553.
[4] 翁艳, 褚云香, 王东盛, 等. CEA、CA125、CA19-9对胃癌的诊断价值及与TNM分期、淋巴结转移的关系[J]. 癌症进展, 2019, 17(5):582-584.
[5] BLONDAL T, JENSBY NIELSEN S, BAKER A, et al. Assessing sample and miRNA profile quality in serum and plasma or other biofluids[J]. Methods, 2013, 59(1):S1-S6.
[6] 杨焕丽, 贾泽博, 梁晓萍, 等. 胃癌患者血清miR-22、miR-20a的水平变化及意义[J]. 山东医药, 2020, 60(31):67-70.
[7] 朱海星, 何新阳. ZNF139通过抑制miR-181a-5p增加胃癌细胞耐药性的机制[J]. 川北医学院学报, 2021, 36(11):1403-1409, 1414.
[8] 顾挺, 刘晓庆, 曹凤, 等. 老年胃癌患者血清中miR-483-5p表达水平及其临床意义[J]. 中华全科医学, 2022, 20(1):8-10, 124.
[9] 柯艺文, 陈绵平, 张馨, 等. 宫颈癌组织中miR-183与GSPT1的表达及临床意义[J]. 临床肿瘤学杂志, 2022, 27(3):210-214.
[10] 刘彤崴, 李良, 王卓, 等. miR-183-5p和NDUFA4L2在肾透明细胞癌中的表达及相关性[J]. 中国医科大学学报, 2023, 52(4):327-332.
[11] SUPIC G, ZELJIC K, RANKOV A D, et al. miR-183 and miR-21 expression as biomarkers of progression and survival in tongue carcinoma patients[J]. Clin Oral Investig, 2018, 22(1):401-409.
[12] SUZUKI R, AMATYA V J, KUSHITANI K, et al. miR-182 and miR-183 promote cell proliferation and invasion by targeting FOXO1 in mesothelioma[J]. Front Oncol, 2018, 8:446.
[13] LIN J, SHEN J, YUE H, et al. miRNA-183-5p.1 promotes the migration and invasion of gastric cancer AGS cells by targeting TPM1[J]. Oncol Rep, 2019, 42(6):2371-2381.
[14] 王娅南, 魏亚宁, 范翔宇, 等. miR-183-5p通过靶向调控FAT1抑制胃癌进展[J]. 华中科技大学学报:医学版, 2022, 51(4):461-466.
[15] LI W, CUI X, QI A L, et al. miR-183-5p acts as a potential prognostic biomarker in gastric cancer and regulates cell functions by modulating EEF2[J]. Pathol Res Pract, 2019, 215(11):152636.
[16] CHEN L X, HUANG X X, ZHANG W Z, et al. Correlation of PD-L1 and SOCS3 co-expression with the prognosis of hepatocellular carcinoma patients[J]. J Cancer, 2020, 11(18):5440-5448.
[17] YAN R, LI K, YUAN D W, et al. miR-183-5p promotes proliferation and migration in hepatocellular carcinoma by targeting IRS1 and its association with patient survival[J]. Int J Biol Markers, 2020, 35(3):83-89.
[18] 蔡晓娟, 王堃, 喻晶. 异常凝血酶原联合CEA、CA72-4和CA199在胃癌诊治中的价值[J]. 肿瘤防治研究, 2018, 45(6):395-399.
[19] ZHAO R, ZHANG Y L, ZHANG X, et al. Exosomal long noncoding RNA HOTTIP as potential novel diagnostic and prognostic biomarker test for gastric cancer[J]. Mol Cancer, 2018, 17(1):68.
[20] TOFT J H, -KLAND I, DALEN I. ROC-curves-fundamentals for proper use[J]. Endocrine, 2022, 76(2):505.