CpG岛甲基化结肠癌临床特点及其在dMMR结肠癌中的预后意义  

Clinical features of CpG island methylation in colon cancer and its prognostic significance in dMMR colon cancer

作　　者：刘媛[1] 王瑞丽[1] 王丹玲[1] 宋建宁[2] Liu Yuan;Wang Ruili;Wang Danling;Song Jianning(Clinical Laboratories Department,Beijing Friendship Hospital,Capital Medical University,Beijng 100050,China;General Surgery Department,Beijing Friendship Hospital,Capital Medical University,Beijng 100050,China)

机构地区：[1]首都医科大学附属北京友谊医院检验科,北京100050 [2]首都医科大学附属北京友谊医院普通外科,国家消化系统疾病中心普外分中心,北京100050

出　　处：《国际外科学杂志》2024年第1期32-37,F0004,共7页International Journal of Surgery

摘　　要：目的探讨CpG岛甲基化(CIMP+)结肠癌的临床特点和预后,以及CIMP状态在错配修复缺陷(dMMR)结肠癌的诊断和预后预测中的指导意义。方法以关键词"colorectal cancer""patient"和"CpG Island Methylator Phenotype"检索基因表达数据库(GEO),得到序列号为GSE39582的数据,共纳入585例结肠癌患者临床资料和肿瘤组织的全转录组测序数据。排除CIMP为缺失值的72例后纳入513例进一步分析,其中男性278例,女性235例,平均年龄(67±13)岁。根据CIMP状态分为CIMP+组(n=93)和CIMP-组(n=420),比较两组临床特点差异,绘制Kaplan-Meier生存曲线比较总生存期和无病生存期差异;提取dMMR亚组71例,分为CIMP+组(n=43)和CIMP-组(n=28),K-M曲线分析两组总生存期和无病生存期差异。组间比较采用t检验、χ^(2)检验或者Mann-WhitneyU非参数检验,生存曲线组间差异性检验采用Long-rank检验。结果CIMP+组患者年龄大于CIMP-组[(70.84±12.60)岁比(66.21±13.08)岁,t=3.18,P=0.002];右半结肠肿瘤起源于CIMP+分子通路途径是左半结肠癌起源于CIMP+的9.3倍(OR=9.3,95%CI:5.2~17.9);BRAF突变型结肠癌起源于CIMP+是BRAF野生型结肠癌起源与CIMP+的215.2倍(OR=215.2,95%CI:53.2~1906.7);dMMR结肠癌患者起源于CIMP+是pMMR患者的12.8倍(OR=12.8,95%CI:7.0~23.9)。CIMP+和CIMP-两组在总生存期和无病生存期方面差异无统计学意义(P=0.590、0.220)。在dMMR结肠癌亚组中,CIMP状态与患者总生存期和无病生存期无相关性(P>0.05)。结论CIMP+结肠癌患病人群多为高龄,肿瘤起源有右半结肠,多合并BRAF基因突变,表现为错配修复缺陷dMMR结肠癌。CIMP状态与结肠癌TNM分期及生存预后无相关性。CIMP+所致dMMR结肠癌与MMR基因突变所致dMMR结肠癌,生存预后无显著差异。Objective To investigate the clinical characteristics and prognosis of CpG island methylator phenotype(CIMP+)colon cancer,and the significance of CIMP status in the diagnosis and prognosis prediction in defective mismatch repair(dMMR)colon cancer.Methods The keywords"colorectal cancer""patient"and"CpG Island Methylator Phenotype"were used to search the Gene Expression Omnibus(GEO)database,and the GSE39582 was obtained,which included the clinical data of 585 patients with colorectal cancer and the sequencing data of the whole transcriptome of the tumor tissues.After excluding 72 cases with missing CIMP values,513 cases were included for further analysis,including 278 males and 235 females,with a mean age of(67±13)years.According to the CIMP status,they were divided into CIMP+group(n=93)and CIMP-group(n=420),then compare the differences in clinical characteristics,the Kaplan-Meier survival curves were plotted to compare the overall survival and disease-free survival;71 dMMR cases were divided into CIMP+group(n=43)and CIMP-group(n=28),and the K-M curves were plotted to analyze the differences in overall survival(OS)and disease free survival(DFS).Comparisons between groups were performed by t-test,χ^(2) test or Mann-Whitney U nonparametric test,and the difference in survival curves was tested by Long-rank test.Results Patients in the CIMP+group were significantly older than those in the CIMP-group[(70.84±12.60)years vs(66.21±13.08)years,t=3.18,P=0.002].Right colon tumors originating from the CIMP+molecular pathway were 9.3 times more likely to be CIMP+than those of the left colon cancers(OR=9.3,95%CI:5.2-17.9).BRAF mutant colon cancer originating from CIMP+was 215.2 times more common than BRAF wild-type colon cancer originating with CIMP+(OR=215.2,95%CI:53.2-1906.7);and patients with dMMR colon cancer originated 12.8 times more common than patients with pMMR(OR=12.8,95%CI:7.0-23.9).The difference between the CIMP+and CIMP-groups was not statistically significant in terms of overall survival and disease-free survi

关 键 词：结肠 肿瘤 基因 突变 CPG岛甲基化 错配修复功能缺失 

分 类 号：R735.35[医药卫生—肿瘤]