Abstract
Background: Lung adenocarcinoma (LUAD) is one of the main types of lung cancer. Because of its low early diagnosis rate, poor late prognosis, and high mortality, it is of great significance to find biomarkers for diagnosis and prognosis.Methods: Five hundred and twelve LUADs from The Cancer Genome Atlas were used for differential expression analysis and short time-series expression miner (STEM) analysis to identify the LUAD-development characteristic genes. Survival analysis was used to identify the LUAD-unfavorable genes and LUAD-favorable genes. Gene set variation analysis (GSVA) was used to score individual samples against the two gene sets. Receiver operating characteristic (ROC) curve analysis and univariate and multivariate Cox regression analysis were used to explore the diagnostic and prognostic ability of the two GSVA score systems. Two independent data sets from Gene Expression Omnibus (GEO) were used for verifying the results. Functional enrichment analysis was used to explore the potential biological functions of LUAD-unfavorable genes.Results: With the development of LUAD, 185 differentially expressed genes (DEGs) were gradually upregulated, of which 84 genes were associated with LUAD survival and named as LUAD-unfavorable gene set. While 237 DEGs were gradually downregulated, of which 39 genes were associated with LUAD survival and named as LUAD-favorable gene set. ROC curve analysis and univariate/multivariate Cox proportional hazards analyses indicated both of LUAD-unfavorable GSVA score and LUAD-favorable GSVA score were a biomarker of LUAD. Moreover, both of these two GSVA score systems were an independent factor for LUAD prognosis. The LUAD-unfavorable genes were significantly involved in p53 signaling pathway, Oocyte meiosis, and Cell cycle.Conclusion: We identified and validated two LUAD-development characteristic gene sets that not only have diagnostic value but also prognostic value. It may provide new insight for further research on LUAD.
Highlights
Lung cancer is the most common cancer (11.6% of the total cases) among men and women in the world, which is the main cause of cancer death (18.4% of the total cancer deaths; Bray et al, 2018)
Multiple Genes Were Defined as lung adenocarcinoma (LUAD)-Development Characteristic Genes
Compared to normal lung tissue samples, there were 3,082 Differentially expressed genes (DEGs) in stage I LUADs, 3,437 DEGs in stage II LUADs, 3,518 DEGs in stage III LUADs, and 3,510 DEGs stage IV LUADs (Figure 2A). It indicated that the gene expression patterns were various with the development of LUAD
Summary
Lung cancer is the most common cancer (11.6% of the total cases) among men and women in the world, which is the main cause of cancer death (18.4% of the total cancer deaths; Bray et al, 2018). Smoking is currently considered to be the main cause of lung cancer. Target therapy is effective for selected advanced LUAD, the overall survival of patients is poor due to the emergence of drug resistance. It has become one of the hot spots in clinical research to find the diagnosis and prognosis indexes of LUAD. Because of its low early diagnosis rate, poor late prognosis, and high mortality, it is of great significance to find biomarkers for diagnosis and prognosis
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