基于TCGA数据库的肺癌和结直肠癌放疗后差异基因筛选、功能及通路研究

Screening and integrative analysis for differentially expressed genes in lung cancer and colorectal cancer after radiotherapy:a study based on TCGA data

目的筛选影响肺癌和结直肠癌放疗敏感性的相关基因及其通路,为患者实现精准放疗提供理论依据。方法从癌症基因组图谱(TCGA)数据库中筛选出肺癌和结直肠癌放疗患者,根据生存期是否超过3年分成两组,进而利用limma软件分析两组患者之间差异表达基因,筛选P<0.05且差异倍数(fold-change,FC)>1.5或FC<0.67的基因并对其进行GO功能注释和KEGG富集、筛选差异表达基因,Kaplan-Meier plotter分析差异表达基因总体生存率。结果从TCGA数据库中筛选出269个上调基因和211个下调基因。其中差异表达基因主要涉及细胞因子细胞因子受体相互作用、Wnt信号通路、细胞色素P450对外来生物代谢的影响等生物过程。主要富集在上皮细胞增殖、细胞细胞黏附的调节、体液免疫反应、对外界刺激反应的积极调节等功能方面。与生存期小于3年的患者相比,SFTPB(P=0.00011)、SFTPA2(P<0.0001)基因低表达的患者生存曲线明显较好,而OLFM4(P=0.00011)、LGALS4(P<0.0001)高表达的患者有更好的生存率。结论SFTPB、SFTPA2、OLFM4和LGALS4可能是影响肺癌和结直肠癌放疗敏感的关键基因。

Objective To screen the genes related to radiation-sensitivity and their pathways in lung cancer and colorectal cancer with bioinformatics.Methods Patients with lung cancer and colorectal cancer after radiotherapy were screened from The Cancer Genome Atlas(TCGA)database.According to the survival≥3 years or<3 years,patients were divided into two groups.The differentially expressed genes between the two groups were analyzed by limma software,and for the differentially expressed genes with fold-change(FC)>1.5 or FC<0.67,the GO function and KEGG enrichment analysis were performed.The overall survival rate of patients with differentially expressed genes was analyzed by Kaplan-Meier plotter.Results A total of 269 up-regulated genes and 211 down-regulated genes were screened out from the TCGA database.The differentially expressed genes were mainly involved in cytokine-cytokine receptor interaction,Wnt signaling pathway,and cytochrome P450.The differentially expressed genes were functionally concentrated in epithelial cell proliferation,regulation of cell-cell adhesion,humoral immune responses,and responses to external stimuli.Patients with low expression of SFTPB(P=0.00011)and SFTPA2(P<0.0001)genes and high expression of OLFM4(P=0.00011)and LGALS4(P<0.0001)genes had a better survival rate.Conclusion SFTPB,SFTPA2,OLFM4 and LGALS4 may be the key genes affecting the radiosensitivity in patients with lung and colorectal cancer.