Abstract
This study aims to determine hub genes related to the incidence and prognosis of EGFR-mutant (MT) lung adenocarcinoma (LUAD) with weighted gene coexpression network analysis (WGCNA). From The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we used 253 EGFR-MT LUAD samples and 38 normal lung tissue samples. At the same time, GSE19188 was additionally included to verify the accuracy of the predicted gene. To discover differentially expressed genes (DEGs), the R package “limma” was used. The R packages “WGCNA” and “survival” were used to perform WGCNA and survival analyses, respectively. The functional analysis was carried out with the R package “clusterProfiler.” In total, 1450 EGFR-MT–specific DEGs were found, and 7 tumor-related modules were marked with WGCNA. We found 6 hub genes in DEGs that overlapped with the tumor-related modules, and the overexpression level of B3GNT3 was significantly associated with the worse OS (overall survival) of the EGFR-MT LUAD patients (p < 0.05). Functional analysis of the hub genes showed the metabolism and protein synthesis–related terms added value. In conclusion, we used WGCNA to identify hub genes in the development of EGFR-MT LUAD. The established prognostic factors could be used as clinical biomarkers. To confirm the mechanism of those genes in EGFR-MT LUAD, further molecular research is required.
Highlights
Lung cancer is the most prominent cancer-related cause of death worldwide
The results of the module–trait relationships revealed that 3 modules in the The Cancer Genome Atlas (TCGA)–epidermal growth factor receptor (EGFR)-MT lung adenocarcinoma (LUAD) and 4 modules in the GSE6631 were found to have an association with tumor tissues (Supplementary Figures S1B, S2B)
The extracted 6 genes in differentially expressed genes (DEGs) that overlapped with the tumor-related modules including beta-1,3N-acetylglucosaminyltransferase 3 (B3GNT3), adhering 3 (CDH3), cysteine SN (CST1), zinc finger and BTB domain containing 16 (ZBTB16), keratin 15 (KRT15), and cloth beta (KLB) were selected as the hub genes for subsequent analysis (Figure 2C)
Summary
Lung cancer is the most prominent cancer-related cause of death worldwide. Non–small-cell lung carcinoma (NSCLC) accounts for 75–80 percent of all lung cancers and is often detected at an early stage, resulting in a poor prognosis (Liu et al, 2017). Lung adenocarcinoma is the most prevalent form of NSCLC (LUAD) (Yang et al, 2020a). Significant advances in the understanding of lung cancer, especially LUAD, have been made in recent years. The epidermal growth factor receptor (EGFR) has been identified as an oncoming engine. In Asian lung adenocarcinoma patients, the frequency of EGFR mutations is higher (Devanagari et al, 2015).
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