Exploring the role of ELOVLs family in lung adenocarcinoma based on bioinformatic analysis and experimental validation.

BACKGROUND

The role of lipid metabolic reprogramming in the development of various types of cancer has already been established. However, the exact biological function and significance of the elongation of very-long-chain fatty acids (ELOVLs) gene family, which can affect fatty acid metabolism, is still not well understood in lung adenocarcinoma (LUAD). The aim of our study is to explore whether there are genes related to the pathogenesis of LUAD in the ELOVLs family, and even to guide clinical medication and potential prognostic indicators.

METHODS

Gene expression profiling interactive analysis (GEPIA), human protein atlas (HPA), cBioPortal, Kaplan-Meier (KM) plotter, single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm and SubMap algorithms were utilized to analyze the role of ELOVLs in the LUAD. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, cell counting kit-8 (CCK8), colony formation, wound healing, transwell migration assays and fatty acid metabolism detection were employed to confirm the significant role of ELOVL6 in vitro experiment.

RESULTS

Our results revealed that mRNA expression levels of ELOVL2, ELOVL4 and ELOVL6 and protein expression levels of ELOVL5 and ELOVL6 were elevated in LUAD tissues compared to normal subjects. The low-expressing ELOVL6 group showed superior overall survival (OS) and disease-specific survival (DSS) versus the high-expressing group. Meanwhile, patients with low-ELOVL6 expression were more sensitive to the 4 representative chemotherapeutic agents. In vitro, we revealed that interfering with ELOVL6 could influence the viability, proliferation, migration capacity and fatty acid metabolism of LUAD cells (A549 and H1299).

CONCLUSIONS

Our study indicated that ELOVL6 could be used as an indicator to evaluate the prognosis and therapeutic effect, and even potential therapeutic target for patients with LUAD.