膀胱尿路上皮癌中候选生物标志物转录因子21的甲基化机制及意义

丁小明 许嵘* 张文州 谢志新

doi:10.16098/j.issn.0529-1356.2019.05.011

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解剖学报 ›› 2019, Vol. 50 ›› Issue (5) : 608-612. DOI: 10.16098/j.issn.0529-1356.2019.05.011

肿瘤生物学

膀胱尿路上皮癌中候选生物标志物转录因子21的甲基化机制及意义

丁小明¹ 许嵘^2* 张文州² 谢志新²

作者信息 +

Methylation mechanism of candidate biomarker transcription factor 21 in bladder urothelial carcinoma

DING Xiao-ming¹XU Rong ^2* ZHANG Wen-zhou²XIE Zhi-xin ²

Author information +

文章历史 +

摘要

目的探讨膀胱尿路上皮癌中候选生物标志物转录因子21（TCF21）甲基化的意义。方法选择2016年10月~2017年10月间疑似膀胱癌患者142例，其中经病理学检测确诊为膀胱癌80例为研究组，经病理学检测确诊为非膀胱癌共62例为对照组。另选择同期进行体检的健康者尿标本40例作为健康组。检测研究组膀胱癌组织、癌旁组织、对照组病灶组织中TCF21甲基化水平，并检测研究组、对照组和健康组尿液中TCF21甲基化水平，分别比较膀胱癌组织、尿液中TCF21甲基化水平与临床病理特点间的关系，并分析两者对于膀胱癌的诊断效能。结果膀胱癌组织TCF21甲基化水平显著高于癌旁组织和对照组（P<0.05），研究组尿液TCF21甲基化水平显著高于对照组和健康组（P<0.05）。男性、年龄>60岁、高的TNM分期和高分级的膀胱癌患者膀胱癌组织和尿液中TCF21甲基化水平更高（P<0.05）。膀胱癌组织与尿液中TCF21甲基化水平对膀胱癌均有较高的诊断意义，且两者的诊断意义差异无显著性（P>0.05）。结论 TCF21基因在膀胱癌组织和膀胱癌患者尿液中均具有较高的甲基化水平，并且与病理特点相关，膀胱癌组织和膀胱癌患者尿液对于膀胱癌均具有较高的诊断意义。

Abstract

Objective To explore the significance of methylation of the candidate biomarker transcription factor 21(TCF21) in bladder urothelial carcinoma. Methods From October 2016 to October 2017, 142 patients with suspected bladder cancer were selected. Among them, 80 were diagnosed as bladder cancer by pathological examination as the study group. A total of 62 non-bladder cancers were diagnosed by pathological examination as the control group. In addition, 40 healthy urine specimens during the same period were selected as the healthy group. Detected and compared the methylation of TCF21 in bladder cancer tissues, paracancerous tissues, and control tissues of the study group, and detected and compared the TCF21 methylation levels in urine of study group, control group, and healthy group. The relationship between TCF21 methylation level and clinicopathological features was explored, and the diagnostic efficacy of both for bladder cancer was analyzed. Results The methylation level of TCF21 in bladder cancer tissue was significantly higher than that in the adjacent tissue and control group (P<0.05). The methylation level of urinary TCF21 in the study group was significantly higher than that in the control and healthy groups (P<0.05). TCF21 methylation levels in bladder cancer tissues and urine were higher in men, ages>60 years, high TNM stages, and high grade bladder cancer patients (P<0.05). TCF21 methylation levels in bladder cancer tissues and urine hadhigher diagnostic efficacy for bladder cancer, and there was no significant difference in the diagnostic efficacy between the two groups (P>0.05). Conclusion TCF21 gene hasd high methylation level in urine of patients with bladder cancer and bladder cancer, and is associated with pathological features. Urinary bladder cancer tissues and urine have higher diagnostic efficacy for bladder cancer.

导出引用

丁小明许嵘张文州谢志新. 膀胱尿路上皮癌中候选生物标志物转录因子21的甲基化机制及意义[J]. 解剖学报. 2019, 50(5): 608-612 https://doi.org/10.16098/j.issn.0529-1356.2019.05.011

DING Xiao-ming XU Rong ZHANG Wen-zhou XIE Zhi-xin. Methylation mechanism of candidate biomarker transcription factor 21 in bladder urothelial carcinoma[J]. Acta Anatomica Sinica. 2019, 50(5): 608-612 https://doi.org/10.16098/j.issn.0529-1356.2019.05.011

参考文献

［1］ Kim JA, Yeom YI. Metabolic signaling to epigenetic alterations in cancer［J］. Biomol Ther, 2018, 26(1):69-80.

［2］ Hanley MP, Hahn MA, Li AX, et al. Genome-wide DNA methylation profiling reveals cancer-associated changes within early colonic neoplasia［J］. Oncogene, 2017, 36(35):5035-5044.

［3］ Zielske SP. Epigenetic DNA methylation in radiation biology: on the field or on the sidelines［J］? J Cell Biochem, 2015, 116(2):212-217.

［4］ Fujimaki T, Oguri M, Horibe H, et al. Association of a transcription factor 21 gene polymorphism with hypertension［J］. Biomed Rep, 2015, 3(1):118-122.

［5］ Sima P, Roth B, Melquist J, et al. A novel role of the transcription factor TCF21 as a suppressor of bladder cancer metastasis［J］. J Urol, 2014, 191(4):e690-e691.

［6］ Edge SB, Compton CC. The American joint committee on cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM［J］. Ann Surg Oncol, 2010, 17(6):1471-1474.

［7］ Wang L, Feng C, Ding G, et al. Relationship of TP53 and Ki67 expression in bladder cancer under WHO 2004 classification［J］. J BUON, 2013, 18(2):420-424.

［8］ Xu R. Methylation of TCF21 gene in bladder cancer and its clinical significance ［D］. Huaqiao University, 2014. (in Chinese)

许嵘.膀胱癌TCF21基因甲基化与临床意义［D］. 华侨大学, 2014.

［9］ Prout GR, Wesley MN, Greenberg RS, et al. Bladder cancer［J］. Cancer, 2015, 89(6):1349-1358.

［10］Bellmunt J, Orsola A, Leow JJ, et al. Bladder cancer: ESMO practice guidelines for diagnosis, treatment and follow-up［J］.Ann Oncol, 2014, Suppl 3: iii40-48.

［11］Shivapurkar N, Stastny Ⅴ, Xie Y, et al. Differential methylation of a short CpG-rich sequence within exon 1 of TCF21 gene: a promising cancer biomarker assay［J］. Cancer Epidemiol, Biomarkers Prev, 2008, 17(4):995-1000.

［12］Yang Z, Li DM, Xie Q, et al. Protein expression and promoter methylation of the candidate biomarker TCF21 in gastric cancer［J］. J Cancer Res Clin Oncol, 2015, 141(2):211-220.

［13］Xin J, Xu R, Lin S, et al. Clinical potential ofTCF21methylation in the diagnosis of renal cell carcinoma［J］. Oncol Lett, 2016, 12(2):1265-1270.

［14］Lin ShK, Xin J, Zhou J, et al. Significance of tumor suppressor gene TCF21 promoter methylation for diagnosis and prognosis of renal cell carcinoma［J］. Cancer Research on Prevention and Treatment, 2016, 43(5):375-381. (in Chinese)

林少坤, 辛军, 周金,等. 抑癌基因TCF21启动子甲基化在肾癌诊断及预后中的意义［J］. 肿瘤防治研究, 2016, 43(5):375-381.

［15］Gooskens SL, Klasson TD, Gremmels H, et al. TCF21 hypermethylation regulates renal tumor cell clonogenic proliferation and migration.［J］. Molecular Oncol, 2018,12(2):166-179.

［16］Yang H, Wang Z, Yong G, et al. Correlation and significance of urinary soluble fas and vascular endothelial growth factor in bladder urothelial cancer［J］. Disease Markers, 2015, 2015(7):1-5.

［17］Kollarik B, Zvarik M, Bujdak P, et al. Urinary fluorescence analysis in diagnosis of bladder cancer.［J］. Neoplasma, 2018, 65(2):234-241.