Lipid metabolic gene-wide profile and survival signature of lung adenocarcinoma 

Abstract Background: Lung cancer is the cancer with high morbidity and mortality across the globe, and lung adenocarcinoma (LUAD) is the most common histologic subtype. The disorder of lipid metabolism is related to the development of cancer. Analysis of lipid-related transcriptome helps shed light on diagnosis and prognostic biomarkers of LUAD. Methods: In this study, we performed an expression analysis of 1045 lipid metabolism-related genes between LUAD tumors and normal tissues from the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort. The interaction network of differential expression genes (DEGs) was constructed to identify. The association between hub genes and overall survival was evaluated and formed a model to predict the prognosis of LUAD using a nomogram, and the model was validated by another cohort (GSE13213). Results: Finally, a total of 217 lipid metabolism-related DEGs were detected in LUAD. They were significantly enriched in Glycerophospholipid metabolism, fatty acid metabolic process, and Eicosanoid Signaling. Then we identified 6 hub genes through network and cytoHubba, including INS, LPL, HPGDS, DGAT1, UGT1A6, and CYP2C9. The high expression of CYP2C9, UGT1A6, and INS, whereas low expressions of DGAT1, HPGDS, and LPL, were associated with worse overall survival (OS) for 1925 LUAD patients. Our model found that the high-risk score group had a worse OS, and the validated cohort had the same result.Conclusion: This study constructed a signature of six lipid metabolic genes, which was significantly associated with the diagnosis and prognosis of LUAD patients. The gene signature can be used as a biomarker for LUAD in the term of lipid metabolic.