Aberrant Methylation and Differential Expression of SLC2A1, TNS4, GAPDH, ATP8A2, and CASZ1 Are Associated with the Prognosis of Lung Adenocarcinoma

Abstract

Lung cancer is one of the leading triggers for cancer death worldwide. In this study, the relationship of the aberrantly methylated and differentially expressed genes in lung adenocarcinoma (LUAD) with cancer prognosis was investigated, and 5 feature genes were identified eventually. Specifically, we firstly downloaded the LUAD-related mRNA expression profile (including 57 normal tissue samples and 464 LUAD tissue samples) and Methy450 expression data (including 32 normal tissue samples and 373 LUAD tissue samples) from the TCGA database. The package “limma” was used to screen differentially expressed genes and aberrantly methylated genes, which were intersected for identifying the hypermethylated downregulated genes (DGs Hyper) and the hypomethylated upregulated genes (UGs Hypo). GO annotation and KEGG pathway enrichment analysis were further performed, and it was found that these DGs Hyper and UGs Hypo were predominantly activated in the biological processes and signaling pathways such as the regulation of vasculature development, DNA-binding transcription activator activity, and Ras signaling pathway, indicating that these genes play a vital role in the initiation and progression of LUAD. Additionally, univariate and multivariate Cox regression analyses were conducted to find the genes significantly associated with LUAD prognosis. Five genes including SLC2A1, TNS4, GAPDH, ATP8A2, and CASZ1 were identified, with the former three highly expressed and the latter two poorly expressed in LUAD, indicating poor prognosis of LUAD patients as judged by survival analysis.