外周血STAT1,STAT3基因启动子CpG岛甲基化状态与大肠癌预后关系的研究

doi:10.11904/j.issn.1002-3070.2019.04.011

摘要/Abstract

摘要： 目的探讨大肠癌(CRC)患者外周血STAT1,STAT3基因启动子CpG岛甲基化状态与大肠癌预后的关系以及影响大肠癌患者预后生存的因素。方法采用队列研究的方法,对哈尔滨医科大学附属肿瘤医院病理确诊的原发性大肠癌住院患者239例进行生物学采样并随访,通过甲基化特异性高分辨率熔解曲线(MS-HRM)分析STAT1,STAT3基因启动子CpG岛甲基化状态。结果 239例大肠癌患者术后1年、3年和5年的生存率分别为为94.90%、86.00%和67.20%。STAT1,STAT3基因甲基化状态与大肠癌患者术后生存期无关(STAT1:HR=0.85,95% CI:0.55~1.30,P=0.44;STAT3:HR=0.75,95% CI:0.36~1.58,P=0.45),Dukes分期(HR=1.31,95% CI:1.14~1.51,P＜0.01)和术中肠吻合器的使用(HR=1.98,95% CI:1.25~3.14,P＜0.01)是影响大肠癌患者预后的重要因素,Dukes分期为C、D期的患者死亡风险显著高于A、B期(HR=1.31,95% CI:1.14~1.51,P＜0.01),术中使用肠吻合器的患者预后优于没有使用肠吻合器的患者。而性别、年龄、肿瘤位置、肿瘤大体分型、组织学分型、术后化疗与大肠癌的预后无关。结论 Dukes分期是影响大肠癌预后生存的独立因素,术中使用肠吻合器患者预后优于未使用者,外周血STAT1,STAT3基因甲基化状态尚不能作为影响大肠癌患者预后的生物标志物。

关键词: 大肠癌, 甲基化, JAK-STAT, 生存分析

Abstract: Objective The aim of this study was to investigate the relationship between STAT1,STAT3 gene promoter CpG island methylation status and prognosis of patients with colorectal cancer(CRC)and the prognostic factors of CRC patients.Methods The cohort study was conducted to biosamples and follow up 239 patients with primary colorectal cancer pathologically diagnosed in Cancer Hospital of Harbin Medical University(Tumor Hospital).The methylation status of STAT1,STAT3 gene promoter CpG island was analyzed by methylation specific high-resolution melting curve(MS-HRM).Results The survival rates of 239 patients with colorectal cancer at 1 year,3 years and 5 years were 94.90%,86.00% and 67.20%,respectively.The methylation status of STAT1 and STAT3 genes was not associated with postoperative survival in colorectal cancer patients(STAT1:HR=0.85,95% CI:0.55~1.30,P=0.44;STAT3:HR=0.75,95% CI:0.36~1.58,P=0.45).Dukes stage(HR=1.31,95% CI:1.14~1.51,P＜0.01)and intraoperative intestinal stapler use(HR=1.98,95% CI:1.25~3.14,P＜0.01)were important factors affecting the prognosis of colorectal cancer patients.The risk of death in patients with stage D and Dukes was significantly higher than that in stages A and B(HR=1.31,95% CI:1.14~1.51,P＜0.01).Intestinal anastomosis was used during operation.The patient′s prognosis was better than that of patients without an intestinal stapler.However,gender,age,tumor location,gross tumor type,histological classification and postoperative chemotherapy were not associated with the prognosis of colorectal cancer.Conclusion Dukes stage is an independent factor affecting the prognosis of colorectal cancer.The prognosis of patients with intestinal stapler is better than that of non-users.The methylation status of STAT1 and STAT3 in peripheral blood is not a biomarkers for the prognosis of patients with colorectal cancer.

Key words: Colorectal cancer, Methylation, JAK-STAT, Survival analysis

中图分类号:

R735.3

普睿, 朱琳, 夏婷婷, 毕皓然, 孙鸿儒, 黄浩, 张磊, 赵亚双. 外周血STAT1,STAT3基因启动子CpG岛甲基化状态与大肠癌预后关系的研究[J]. 实用肿瘤学杂志, 2019, 33(4): 346-351.

PU Rui, ZHU Lin, XIA Tingting, BI Haoran, SUN Hongru, HUANG Hao, ZHANG Lei, ZHAO Yashuang. Relationship between the methylation status of CpG island in STAT1,STAT3 gene promoters in peripheral blood and prognosis of colorectal cancer[J]. Journal of Practical Oncology, 2019, 33(4): 346-351.

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