Ren Jin, Yang Yun, Li Chuanyin, Xie Lu, Hu Ronggui, Qin Xiong, Zhang Menghuan
School of Medicine, Guizhou University, Guiyang, China.
Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Front Genet. 2021 Jan 21;11:634634. doi: 10.3389/fgene.2020.634634. eCollection 2020.
Lung adenocarcinoma (LUAD) is caused by multiple biological factors. Therefore, it will be more meaningful to study the prognosis from the perspective of omics integration. Given the significance of epigenetic modification and immunity in tumorigenesis and development, we tried to combine aberrant methylation and tumor infiltration CD8 T cell-related genes to build a prognostic model, to explore the key biomarkers of early-stage LUAD. On the basis of RNA-seq and methylation microarray data downloaded from The Cancer Genome Atlas (TCGA), differentially expressed genes and aberrant methylated genes were calculated with "DEseq2" and "ChAMP" packages, respectively. A Chi-square test was performed to obtain methylation driver genes. Weighted correlation network analysis (WGCNA) was utilized to mine cancer biomarkers related to CD8 T cells. With the consequences of univariate Cox proportional hazards analysis and least absolute shrinkage and selection operator (LASSO) COX regression analysis, the prognostic index based on 17 methylation driver genes (ZNF677, FAM83A, TRIM58, CLDN6, NKD1, NFE2L3, FKBP5, ITGA5, ASCL2, SLC24A4, WNT3A, TMEM171, PTPRH, ITPKB, ITGA2, SLC6A17, and CCDC81) and four CD8 T cell-related genes (SPDL1, E2F7, TK1, and TYMS) was successfully established, which could make valuable predictions for the survival risk of patients with early-stage LUAD.
肺腺癌(LUAD)由多种生物学因素引起。因此,从组学整合的角度研究预后将更有意义。鉴于表观遗传修饰和免疫在肿瘤发生发展中的重要性,我们试图将异常甲基化和肿瘤浸润性CD8 T细胞相关基因相结合,构建一个预后模型,以探索早期LUAD的关键生物标志物。基于从癌症基因组图谱(TCGA)下载的RNA测序和甲基化微阵列数据,分别使用“DEseq2”和“ChAMP”软件包计算差异表达基因和异常甲基化基因。进行卡方检验以获得甲基化驱动基因。利用加权基因共表达网络分析(WGCNA)挖掘与CD8 T细胞相关的癌症生物标志物。根据单因素Cox比例风险分析和最小绝对收缩和选择算子(LASSO)COX回归分析的结果,成功建立了基于17个甲基化驱动基因(ZNF677、FAM83A、TRIM58、CLDN6、NKD1、NFE2L3、FKBP5、ITGA5、ASCL2、SLC24A4、WNT3A、TMEM171、PTPRH、ITPKB、ITGA2、SLC6A17和CCDC81)和4个CD8 T细胞相关基因(SPDL1、E2F7、TK1和TYMS)的预后指数,该指数可为早期LUAD患者的生存风险做出有价值的预测。