TNF-α和FOXA2蛋白在结直肠癌组织中的表达及其临床意义

doi:10.3969/j.issn.1004-616x.2023.04.009

摘要/Abstract

摘要： 目的：研究肿瘤坏死因子α(TNF-α)和叉头框蛋白A2(FOXA2)蛋白在结直肠癌组织中的表达情况，探讨其与结直肠癌患者临床病理指标的关系。方法：收集结直肠癌及配对癌旁正常组织39例，选取同期经结肠镜切除并经病理证实的结直肠腺瘤组织42例。采用免疫组织化学技术检测结直肠组织中TNF-α和FOXA2蛋白的表达情况，Spearman法分析二者表达的相关性，卡方检验分析TNF-α和FOXA2蛋白表达与结直肠癌患者临床病理指标的关系。结果：TNF-α蛋白在正常结直肠黏膜、结直肠腺瘤及结直肠癌组织中的阳性表达率分别为23.08%、50%和76.92%，组间比较的差异有统计学意义(P<0.05)；FOXA2蛋白在正常结直肠黏膜、结直肠腺瘤及结直肠癌组织中的阳性表达率分别为23.08%、52.38%和79.49%，组间比较的差异有统计学意义(P<0.05)。TNF-α蛋白表达在不同直径、组织学类型腺瘤组织间的差异有统计学意义(P<0.05)，FOXA2蛋白的表达在不同直径、形状类型腺瘤组织间的差异有统计学意义(P<0.05)。在结直肠癌组织中，TNF-α蛋白表达在不同分化程度、浸润深度、淋巴结转移及TNM分期组间比较的差异均有统计学意义(P<0.05)，FOXA2蛋白表达在不同分化程度、淋巴结转移、TNM分期组间比较的差异均有统计学意义(P<0.05)。结直肠癌组织中TNF-α和FOXA2表达存在正相关，相关系数r_s=0.475(P<0.05)。结论：TNF-α和FOXA2蛋白在正常肠黏膜、结直肠腺瘤及结直肠癌组织中的阳性表达率呈逐渐上升趋势，提示TNF-α、FOXA2蛋白与结直肠癌的发生、发展密切相关。肿瘤分化程度越差，浸润深度越深，伴淋巴结转移率越高及TNM分期越晚，TNF-α蛋白阳性表达率越高，提示TNF-α蛋白可能在结直肠癌的发生发展过程中起促进作用。肿瘤分化程度越差，淋巴结转移率越高及TNM分期越晚，FOXA2蛋白阳性表达率越高，提示FOXA2蛋白可能在结直肠癌的发生发展过程中起促进作用。

关键词: 结直肠癌, 结直肠腺瘤, 肿瘤坏死因子α, 叉头框蛋白A2

Abstract: OBJECTIVE： To investigate relationships between expression of TNF-α and FOXA2 proteins in colorectal cancer tissues，and clinicopathologic indexes in the patients. METHODS： Thirty-nine cases of colorectal cancer and paired paracancer normal tissues (more than 5 cm from the tumor margin) were collected，and 42 cases of colorectal adenoma tissues which were confirmed by pathology and colonoscopy were selected. Immunohistochemistry was used to determine expression of TNF-α and FOXA2 proteins in colorectal tissue，using the Spearman method for evaluation. The Chi-square test was used to analyze relationships between the expression of TNF-α and FOXA2 protein，and clinicopathologic indexes in the colorectal cancer patients. RESULTS： The positive expression rates for the TNF-α protein in normal colorectal mucosa，colorectal adenoma and colorectal cancer tissues were 23.08%，50% and 76.92%，respectively，and the differences among the groups were statistically significant. The positive expression rates for the FOXA2 protein in the three tissues were 23.08%，52.38% and 79.49%，respectively，and the differences were statistically significant. There were statistically significant differences in expressions of the TNF-α and of the FOXA2 proteins among different diameter and histological types of adenomas (P<0.05). In colorectal cancer tissues，there were statistically significant differences in TNF-α protein expression among different degrees of differentiation，depth of invasion，lymph node metastasis and TNM staging，while there were statistically significant differences in FOXA2 protein expression among different degrees of differentiation，lymph node metastasis and TNM staging (P<0.05). The expressions of TNF-α and FOXA2 were positively correlated with rs=0.475 (P<0.05). CONCLUSION： The positive expression rates of TNF-α and FOXA2 proteins were different in normal intestinal mucosa，colorectal adenoma and colorectal cancer tissues，with gradually increasing trend，suggesting that TNF-α and FOXA2 proteins were closely related to the occurrence and development of colorectal cancers. Higher positive expression rates of TNF-α were associated with worse tumor differentiation，deeper depth of invasion，higher rates of lymph node metastasis and later TNM stages. The strong associations suggest that TNF-α protein played a promoting role in the occurrence and development of colorectal cancers. Similarly，higher the FOXA2 positive expression rates were associated with worse tumor differentiation，higher lymph node metastasis rates and later TNM stages，suggesting that FOXA2 protein was also involved with the occurrence and development of colorectal cancers.

Key words: colorectal cancer, colorectal adenoma, tumor necrosis factor, forkhead box protein A2

中图分类号:

R735.3

黄梦盼, 王学红, 芦永福. TNF-α和FOXA2蛋白在结直肠癌组织中的表达及其临床意义[J]. 癌变·畸变·突变, 2023, 35(4): 296-301,324.

HUANG Mengpan, WANG Xuehong, LU Yongfu. Expression and clinical significance of TNF-α and FOXA2 in patients with colorectal cancer[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(4): 296-301,324.

参考文献

[1] RAWLA P, SUNKARA T, BARSOUK A. Epidemiology of colorectal cancer: incidence, mortality, survival, and risk factors[J]. Prz Gastroenterol, 2019, 14(2): 89-103.
[2] KALTENBACH T, ANDERSON J C, BURKE C A, et al. Endoscopic removal of colorectal lesions-recommendations by the US multi-society task force on colorectal cancer[J]. Gastroenterology, 2020, 158(4): 1095-1129.
[3] MURATA M. Inflammation and cancer[J]. Environ Health Prev Med, 2018, 23(1): 50.
[4] AL OBEED O A, ALKHAYAL K A, SHEIKH A A, et al. Increased expression of tumor necrosis factor-α is associated with advanced colorectal cancer stages[J]. World J Gastroenterol, 2014, 20(48): 18390-18396.
[5] LI Q R, WU H L, CAO M M, et al. Colorectal cancer burden, trends and risk factors in China: a review and comparison with the United States[J]. Chung Kuo Yen Cheng Yen Chiu, 2022, 34(5): 483-495.
[6] ZHANG L, CAO F, ZHANG G Y, et al. Trends in and predictions of colorectal cancer incidence and mortality in China from 1990 to 2025[J]. Front Oncol, 2019, 9: 98.
[7] 于秀冰, 夏志坤, 丁保锋. 结直肠癌患者组织TNF-α、MCP-1表达水平与病理进展的相关性[J]. 临床和实验医学杂志, 2022, 21(5): 505-508.
[8] 禹蓉, 董卫国, 田山, 等. 不同病理类型结直肠息肉癌变的临床研究进展[J]. 中国全科医学, 2023, 26(14): 1790-1794.
[9] SHORT M, LAYTON M C, TEER B, et al. Colorectal cancer screening and surveillance[J]. American family physician, 2015, 91(2): 93-100.
[10] LIEBERMAN D A, REX D K, WINAWER S J, et al. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer[J]. Gastroenterology, 2012, 143(3): 844-857.
[11] 龙华婧, 夏阳, 刘道利, 等. 血清TNF-α在结直肠癌患者中的临床价值研究[J]. 国际检验医学杂志, 2017, 38(10): 1319-1321.
[12] STANILOV N, MITEVA L, DOBREVA Z, et al. Colorectal cancer severity and survival in correlation with tumour necrosis factor-alpha[J]. Biotechnol Biotechnol Equip, 2014, 28(5): 911-917.
[13] LIU M, LEE D F, CHEN C T, et al. IKKα activation of NOTCH links tumorigenesis via FOXA2 suppression[J]. Mol Cell, 2012, 45(2): 171-184.
[14] YANG Z, JIANG X D, ZHANG Z H, et al. HDAC3-dependent transcriptional repression of FOXA2 regulates FTO/m⁶A/MYC signaling to contribute to the development of gastric cancer[J]. Cancer Gene Ther, 2021, 28(1/2): 141-155.
[15] CAMOLOTTO S A, PATTABIRAMAN S, MOSBRUGER T L, et al. FoxA1 and FoxA2 drive gastric differentiation and suppress squamous identity in NKX2-1-negative lung cancer[J]. Elife, 2018, 7: e38579.
[16] SALEM M, O’BRIEN J A, BERNAUDO S, et al. miR-590-3p promotes ovarian cancer growth and metastasis via a novel FOXA2-versican pathway[J]. Cancer Res, 2018, 78(15): 4175-4190.
[17] SONG Y, WASHINGTON M K, CRAWFORD H C. Loss of FOXA1/2 is essential for the epithelial-to-mesenchymal transition in pancreatic cancer[J]. Cancer Res, 2010, 70(5): 2115-2125.
[18] 彭好. Foxa2在结直肠息肉和结直肠癌中的表达及其意义[J]. 胃肠病学, 2019, 24(11): 655-659.
[19] VAN DOORN S C, HAZEWINKEL Y, EAST J E, et al. Polyp morphology: an interobserver evaluation for the Paris classification among international experts[J]. Am J Gastroenterol, 2015, 110(1): 180-187.
[20] WANG B L, LIU G W, DING L, et al. FOXA2 promotes the proliferation, migration and invasion, and epithelial mesenchymal transition in colon cancer[J]. Exp Ther Med, 2018, 16(1): 133-140.
[21] DEBNATH P, HUIREM R S, DUTTA P, et al. Epithelial-mesenchymal transition and its transcription factors[J]. Biosci Rep, 2022, 42(1): BSR20211754.
[22] LU W, KANG Y B. Epithelial-mesenchymal plasticity in cancer progression and metastasis[J]. Dev Cell, 2019, 49(3): 361-374.