结直肠癌免疫相关基因预后模型的构建与验证

Construction and validation of prognosis model of immune related genes in colorectal cancer

目的通过构建结直肠癌免疫相关基因预后模型用于评估患者预后。方法从基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库下载基因表达数据和临床信息,筛选其中差异表达的免疫相关基因。基于单因素和多因素Cox回归分析建立风险模型,进一步分析该模型对于临床预后评估的应用价值,并通过外部数据集对模型进行验证。结果共鉴定出85个免疫相关差异表达基因。筛选C-X-C基序趋化因子配体3(CXCL3)、脂联素受体蛋白1(ADIPOQ)、鸟嘌呤核苷酸结合蛋白G(i)亚基α-1(GNAI1)、上皮细胞特异性分子1(ESM1)、锯齿状蛋白2(JAG2)、白血病抑制因子(LIF)、血管活性肠肽(VIP)、盐皮质激素受体(NR3C2)共8个基因建立风险模型。基于该模型获得患者风险评分,高风险组预后差于低风险组(χ^(2)=22.611,P<0.001),且该风险评分为结直肠癌患者独立预后因素[风险比(HR)=1.154,95%可信区间(CI):1.091~1.220,P<0.001)。该模型的受试者工作特征曲线下面积为0.763,可以较好地区分高低风险的结直肠癌患者。结论本研究成功构建结直肠癌免疫相关基因预后模型,为预测结直肠癌患者预后提供新方法。

Objective To evaluate the prognosis of colorectal cancer patients by constructing the prognosis model of immune related genes.Methods Gene expression data and clinical information were downloaded from Gene Expression Omnibus and The Cancer Genome Atlas.The differentially expressed immune related genes were screened.The prognostic risk model was established based on univariate and multivariate Cox regression analysis.Furthermore,the application value of the model for clinical prognosis evaluation was analyzed.The model was validated by external datasets.Results A total of 85 differentially expressed immune-related genes were identified.Eight genes including C-X-C motif chemokine ligand 3(CXCL3),adiponectin receptor protein 1(ADIPOQ),guanine nucleotide-binding protein G(i)subunit alpha-1(GNAI1),endothelial cell-specific molecule 1(ESM1),protein jagged-2(JAG2),leukemia inhibitory factor(LIF),vasoactive intestinal peptide(VIP),mineralocorticoid receptor(NR3C2)were screened to establish a risk model.The risk score based on the model was significantly correlated with the overall survival rate.The prognosis of the high-risk group was worse than that of the low-risk group(χ^(2)=22.611,P<0.001).The risk score was an independent prognostic factor for colorectal cancer patients[hazard ratio(HR)=1.154,95%confidence interval:1.091-1.220,P<0.01].The area under receiver operating characteristic(ROC)curve for this model is 0.763,which can be used to distinguish high risk and low risk colorectal cancer patients.Conclusion This study successfully constructed the prognosis model of colorectal cancer based on the immune related genes,which provides a new method for predicting the prognosis of colorectal cancer patients.