A Novel Prognostic Model of Early-Stage Lung Adenocarcinoma Integrating Methylation and Immune Biomarkers.

A Novel Prognostic Model of Early-Stage Lung Adenocarcinoma Integrating Methylation and Immune Biomarkers.
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整合甲基化和免疫生物标志物的早期肺腺癌的新预后模型

DOI:
10.3389/fgene.2020.634634
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发表时间:
2020
影响因子:
3.7
通讯作者:
Zhang M
Zhang M
中科院分区:
生物学3区
文献类型:
--
作者:
Ren J;Yang Y;Li C;Xie L;Hu R;Qin X;Zhang M

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肺腺癌(LUAD)是由多种生物学因素引起的。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意义,本研究尝试将联合收割机异常甲基化和肿瘤浸润CD 8 T细胞相关基因结合起来,构建预测模型,探索LUAD早期的关键生物标志物。基于从癌症基因组图谱(TCGA)下载的RNA-seq和甲基化微阵列数据,分别用“DEseq 2”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。利用加权相关网络分析(WGCNA)来挖掘与CD 8 T细胞相关的癌症生物标志物。通过单因素考克斯比例风险分析和最小绝对收缩选择算子(LASSO)考克斯回归分析,(ZNF 677、FAM 83A、TRIM 58、CLDN6、NKD 1、NFE 2L3、FKBP 5、ITGA 5、ASC L2、SLC 24 A4、WNT 3A、TMEM 171、PTPRH、ITPKB、ITGA 2、SLC 6A17、和CCDC 81)和4个CD 8 T细胞相关基因(SPDL 1、E2 F7、TK 1和TYMS)的表达,对预测早期LUAD患者的生存风险具有重要意义。
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.
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CD8+ T细胞和CD4+ T细胞的同时浸润是非小细胞肺癌中的一个有利的预后因素。
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