FOLFOX耐药相关基因是预测结肠癌患者预后的潜在生物标志物  

FOLFOX resistance-associated gene,a potential biomarker for predicting the prognosis of colon cancer patients

作　　者：陈曙冉 董锐 吴华彰 刘牧林[1,2] CHEN Shuran;DONG Rui;WU Huazhang;LIU Mulin(Department of Gastroenterology,the First Affiliated Hospital of Bengbu Medical College,Bengbu,Anhui 233000,China;School of Life Science,Anhui Province Key Laboratory of Translational Cancer Research,Bengbu Medical College,Bengbu,Anhui 233000,China)

机构地区：[1]蚌埠医学院第一附属医院胃肠外科,安徽蚌埠233000 [2]蚌埠医学院生命科学学院癌症转化医学安徽省重点实验室,安徽蚌埠233000

出　　处：《重庆医学》2022年第17期3016-3024,共9页Chongqing medicine

基　　金：安徽省自然科学基金项目(2108085MH291);蚌埠医学院512人才培养计划项目(by51201107);蚌埠医学院自然科学基金项目(2020byzd153);蚌埠医学院研究生科研创新计划项目(Byycx21084)。

摘　　要：目的探索结肠癌对FOLFOX化疗方案耐药的关键机制。方法综合GEO数据库中FOLFOX化疗方案相关数据集,合并后筛选差异表达基因,随机森林树提取特征基因作为耐药核心基因,评估其与临床药物的敏感性关系。共识聚类区分耐药核心基因的亚型及亚型的差异基因集,构建基于TCGA和GSE29621数据的风险模型,评估耐药核心基因与患者临床病理特征和预后的联系。结果随机森林树筛选出来的耐药核心基因的表达水平能明显将对FOLFOX化疗方案反应与否的患者区分开来。分型结果显示主要的耐药原因为免疫浸润,使用耐药相关基因构建的风险模型比常规TNM分期更能预测患者的预后,且高低风险组患者的免疫浸润程度和免疫细胞水平具有明显差异。结论FOLFOX化疗耐药与结肠癌患者的免疫浸润密切相关,耐药相关基因构建的风险模型能较好预测患者的临床病理转归和预后。Objective To explore the key resistance mechanism of colon cancer to FOLFOX chemotherapy regimen.Methods The datasets related to the FOLFOX chemotherapy regimen in the GEO database were merged,and differentially expressed genes were screened.The core genes related to drug resistance were extracted from random forest trees.Their relationships with clinical drug sensitivity were also evaluated.Consensus clustering distinguished subtypes of resistance core genes and differential gene sets of subtypes.Based on TCGA and GSE29621 data,a risk model was constructed to assess the association of drug resistance core genes with patient clinicopathological characteristics and prognosis.Results The expression levels of core resistance genes screened from random forest trees significantly distinguished patients who responded to the FOLFOX regimen.The genotyping results showed that immunologic invasion was the main cause of drug resistance.The risk model could effectively predict the prognosis of colon cancer patients compared with routine TNM staging.The degree of immune infiltration and the content of immune cells were significantly different between the high-risk and low-risk groups.Conclusion FOLFOX resistance were closely associated with the immune invasion in the colon cancer patients.Moreover,the risk model constructed from drug resistance-related genes can predict the clinicopathological outcome and prognosis of the colon cancer patients.

关 键 词：FOLFOX 结肠癌 预后模型 耐药 肿瘤免疫 生物信息学 

分 类 号：R735.3[医药卫生—肿瘤]