基于数据库对结肠癌预后模型的构建与临床验证

Construction and clinical verification of colon cancer prognosis model based on database

目的运用生物信息分析的方法寻找新的靶向基因预测结肠癌的预后情况,为结肠癌的诊断及临床治疗提供新的思路。方法通过对GEO和TCGA数据库联合分析差异基因,进行富集通路后绘制蛋白网络互作图筛选关键基因。验证集验证关键基因表达情况,行Cox回归生存分析,ROC评估关键基因对结肠癌的诊断和预后预测能力,绘制列线图模型。免疫组化验证关键基因的表达情况,分析其与临床预后情况。结果共有293个差异基因,可能参与Wnt/β-cantenin通路、PPAR通路和趋化因子相关的炎症信号通路等,进一步筛选出包含ITM2C、LRRC19、C1orf115、TMEM236等4个基因的模块,Cox回归分析发现ITM2C是结肠癌的独立预后因素,ITM2C高表达的患者具有更好的总体生存期(P<0.05)。ROC曲线显示ITM2C基因对结肠癌有较好的诊断能力(AUC=0.983),1、3、5年时间依赖ROC曲线下面积分别为0.54、0.54、0.65。构建了ITM2C相关的生存预测模型,校准曲线显示该模型有较好的预测能力。免疫组化验证了ITM2C在结肠癌组织中低表达(P<0.05),生存分析证实了ITM2C高表达组的生存优于低表达组。结论ITM2C在结肠癌组织中低表达,且影响患者预后,该基因可作为结肠癌诊断和预后评估的潜在靶点。

Objective To identify new targeted genes for predicting the prognosis of colon cancer by bioinformatics analysis,and to provide fress insights for the diagnosis and clinical treatment of colon cancer.Methods The GEO and TCGA database colon cancer datasets were jointly analyzed for differential genes,and the protein network interaction map was drawn to screen key genes for enrichment pathway analysis.The external validation set verified the expression of key genes,performed Cox regression to analyze the prognosis,ROC evaluated the ability of key genes to diagnose and predict prognosis of colon cancer,and drew a nomogram model.Finally,immunohistochemical experiments verified the expression of key genes,and analyzed their relationship with clinical prognosis.Results A module containing 4 genes including ITM2C,LRRC19,C1orf115,and TMEM236 was screened out,and the enrichment analysis of the key genes in the module found that ITM2C may be involved in the synthesis of immunoglobulin A,and affect the secretion of digestive juice,etc.Cox regression analysis found that ITM2C was an independent factor affecting the prognosis of colon cancer.Patients with high ITM2C expression had better overall survival(P<0.05).The ROC curve showed that the ITM2C gene had a good diagnostic ability for colon cancer(AUC=0.983),and the AUC of time-dependent ROC curve of 1,3,and 5-year survival rates were 0.54,0.54 and 0.65,respectively.Finally,immunohistochemical experiments verified the low expression of ITM2C in colon cancer tissues(P<0.05),and clinical case data confirmed that the survival rate of the ITM2C high expression group was better than that of the low expression group.Conclusion The expression of ITM2C is low in colon cancer,and its expression may affect the prognosis.It can be used as a potential target for the diagnosis and treatment of colon cancer.