Comprehensive Analysis of TCGA LUAD and LUSC Cohorts

The clinical information, RNA expression, mutational status and protein array of The Cancer Genome Atlas Lung Adenocarcinoma (TCGA LUAD) and Lung Squamous Cell Carcinoma (LUSC) patients were retrieved from TCGA database. The patients with EGFR exon 18–21 mutations and ALK gene fusions were filtered to avoid make a disturbance for the analysis. In the signature score analysis, the expression of genes in a signature was normalized in the form of fragments per kilobase of exon model per million mapped fragments (FPKM). Then, a principal component analysis (PCA) was performed, and PC1 was extracted to serve as gene signature score (34). The 18 signatures and their gene sets were summarized from published papers (34–38). The significantly differential expression analysis was based on DESeq2 (39). The row counts of LUAD and LUSC patients were used as input for DESeq2. The differential expression genes were defined as the genes with absolutely log2Foldchange ≥ 1 and p-value ≤ 0.05. The oncoplot of top 30 mutated genes were drawn by using R package maftools (31).