Abstract

BackgroundAlterations in lipid metabolism are increasingly being recognized. However, the application of lipid metabolism in the prognosis of gastric cancer (GC) has not yet been explored.MethodsA total of 204 lipid metabolism relative genes were analyzed in the GC cohort from The Cancer Genome Atlas (TCGA), and four independent cohorts from Gene Expression Omnibus (GEO) and one cohort from Wuhan Union Hospital were applied for external validation. Differential expression and enrichment analyses were performed between GC and normal tissue. The LASSO-Cox proportional hazard regression model was applied to select prognostic genes and to construct a gene expression profile.ResultsOur research indicated that higher expression level of AKR1B1, PLD1, and UGT8 were correlated with worse prognosis of GC patients, while AGPAT3 was correlated with better prognosis. Furthermore, we developed a gene profile composed of AGPAT3, AKR1B1, PLD1, and UGT8 suggested three groups with a significant difference in overall survival (OS). The profile was successfully validated in an independent cohort and performed well in the immunohistochemical cohort. Furthermore, we found that ether lipid metabolism, glycerophospholipid metabolism, and glycerolipid metabolism were upregulated, and fatty acid β-oxidation and other lipid peroxidation processes were reduced in GC.ConclusionCollectively, we found lipid metabolism is reliable and clinically applicable in predicting the prognosis of GC based on a novel gene profile.

Highlights

  • Gastric cancer (GC) is a leading cause of cancer-related death, especially in Eastern Asia [1,2,3]

  • Our research indicated that higher expression level of AKR1B1, PLD1, and UGT8 were correlated with worse prognosis of GC patients, while AGPAT3 was correlated with better prognosis

  • We found that ether lipid metabolism, glycerophospholipid metabolism, and glycerolipid metabolism were upregulated, and fatty acid b-oxidation and other lipid peroxidation processes were reduced in GC

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Summary

Introduction

Gastric cancer (GC) is a leading cause of cancer-related death, especially in Eastern Asia [1,2,3]. Alterations in lipid metabolism in cancer cells have received increasing attention and recognition. Lipogenesis, for example, is strongly upregulated to satisfy the demands of increased membrane biogenesis in malignant tumors [9], and lipid uptake and storage are disproportionately elevated [10, 11]. Targeting these pathway-regulating lipid metabolisms has become a novel anticancer strategy. The application of lipid metabolism in the prognosis of gastric cancer (GC) has not yet been explored

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