Bioinformatics and integrated analyses of prognosis-associated key genes in lung adenocarcinoma

Background: The objective of the present study was to predict candidate genes with prognostic information for lung adenocarcinoma (LUAD).

Methods: Weighted correlation network analysis (WGCNA) was utilized to build the co-expression network of deferentially expressed genes (DEGs) in GSE32863. Key genes were identified as the intersecting genes of the modules of WGCNA and DEGs. Kaplan-Meier plotter was employed to conduct survival analysis. Enrichment analysis was performed. The expression of key genes in LUAD was validated. Then, we performed in vitro experiments to explore functions of key genes. We overexpressed DYNLRB2 in A549 cell. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were test expression levels and functional analyses were performed, including cell viability, Apoptosis.

Results: A total of 1,587 DEGs in GSE32863 were identified, including 649 up-regulated genes and 938 down-regulated genes. In coexpression analysis, there were 1,271 hubgenes from the modules that were chosen for further analysis. 15 key genes were identified as the intersecting genes of the modules of WGCNA and DEGs. The expressions of dynein light chain roadblock-type 2 (DYNLRB2) and mouse homolog of ß1 spectrin (SPTBN1) were lower in LUAD, and were associated with survival time of LUAD patients. GSEA results showed that high expressed DYNLRB2 and SPTBN1 were enriched in Drug metabolism Cytochrome P450, Cardiac muscle contraction, Retinol metabolism. Down-regulated DYNLRB2 and SPTBN1 were associated with Homologous recombination, Progesterone mediated oocyte maturation, Base excision repair. The in vitro experiment confirmed the overexpression of DYNLRB2 in A549 transferred cells. The overexpress DYNLRB2 inhibited cell viability and induced Apoptosis.

Conclusions: Our study suggested that DYNLRB2 and SPTBN1 might be potential tumor suppressor genes and could serve as biomarkers for predicting the prognosis of LUAD patients.