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

Abstract

Background: Lung cancer has high morbidity and mortality across the globe, and lung adenocarcinoma (LUAD) is the most common histologic subtype. A disordered lipid metabolism is related to the development of cancer. Analysis of lipid-related transcriptome helps shed light on the diagnosis and prognostic biomarkers of LUAD. Methods: In this study, expression analysis of 1045 lipid metabolism-related genes was performed between LUAD tumors and normal tissues derived from the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) cohort. The interaction network of differentially-expressed genes (DEGs) was constructed to identify the hub genes. The association between hub genes and overall survival (OS) was evaluated and formed a model to predict the prognosis of LUAD using a nomogram. The model was validated by another cohort, GSE13213. Results: A total of 217 lipid metabolism-related DEGs were detected in LUAD. Genes were significantly enriched in glycerophospholipid metabolism, fatty acid metabolic process, and eicosanoid signaling. Through network analysis and cytoHubba, 6 hub genes were identified, including INS, LPL, HPGDS, DGAT1, UGT1A6, and CYP2C9. High expression of CYP2C9, UGT1A6, and INS, and low expressions of DGAT1, HPGDS, and LPL, were associated with a worse overall survival for 1925 LUAD patients. The model showed that the high-risk score group had a worse OS, and the validated cohort showed the same result. Conclusions: In this study, a signature of 6 lipid metabolism genes was constructed, which was significantly associated with the diagnosis and prognosis of LUAD patients. Thus, the gene signature can be used as a biomarker for LUAD.

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“…Respectively, 372 and 324 amino metabolism-related and glucose metabolism-related genes were attained. Lipid metabolism-related genes were collected from the Kyoto Encyclopedia of Genes and Genomes (KEGG) website (http://www.kegg.jp/blastkoala/) and the Molecular Signatures Database (MSigDB) website (https:// www.gseamsigdb.org/gsea/msigdb/index.jsp) [14]. 1045 lipid metabolism-related genes were finally included in analysis (Supplementary table 1.1-1.3).…”