Abstract
Purpose: The aim of the present study was to screen differential metabolites of gastric cancer (GC) and identify the key metabolic pathways of GC.Methods: GC (n=28) and matched paracancerous (PC) tissues were collected, and LC-MS/MS analysis were performed to detect metabolites of GC and PC tissues. Metabolite pathways based on differential metabolites were enriched by MetaboAnalyst, and genes related to metabolite pathways were identified using the KEGGREST function of the R software package. Transcriptomics data from The Cancer Genome Atlas (TCGA) was analyzed to obtain differentially expressed genes (DEGs) of GC. Overlapping genes were acquired from metabonimics and transcriptomics data. Pathway enrichment analysis was performed using String. The protein expression of genes was validated by the Human Protein Atlas (HPA) database.Results: A total of 325 key metabolites were identified, 111 of which were differentially expressed between the GC and PC groups. Seven metabolite pathways enriched by MetaboAnalyst were chosen, and 361 genes were identified by KEGGREST. A total of 2831 DEGs were identified from the TCGA cohort. Of these, 1317 were down-regulated, and 1636 were up-regulated. Twenty-two overlapping genes were identified between genes related to metabolism and DEGs. Glycerophospholipid (GPL) metabolism is likely associated with GC, of which AGPAT9 and ETNPPL showed lower expressed in GC tissues.Conclusions: We investigated the tissue-based metabolomics profile of GC, and several differential metabolites were identified. GPL metabolism may affect on progression of GC.
Highlights
Gastric cancer (GC) is one of the most common malignant tumors and ranks fifth as the cause of death among 36 cancers in the world [1]
Twenty-two genes related to metabolites were identified based on metabolomics analysis with the help of The Cancer Genome Atlas (TCGA) transcriptomics data
GPL metabolism, which involves in six genes (PLA2G2C, PLA2G4D, PLA2G12B, ETNPPL, DGKB, and AGPAT9) and two metabolites, is likely associated with GC
Summary
Gastric cancer (GC) is one of the most common malignant tumors and ranks fifth as the cause of death among 36 cancers in the world [1]. 50% of cancer patients in China have gastrointestinal tumors, mainly in GC, and the 5-year survival rate is less than 35% [2]. The 5-year survival rate of patients with advanced GC is less than 20%, but it may reach more than 90% if it only invades the mucosal or submucosal layer [4]. GC has no specific clinical symptoms in the early stage, and most patients are in the middle and advanced stage when diagnosed, which leads to a poor prognosis. It is imperative to explore the mechanism of GC and identify biomarkers for early diagnosis
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