Integration of transcriptomics, proteomics, and metabolomics data to reveal HER2-associated metabolic heterogeneity in gastric cancer with response to immunotherapy and neoadjuvant chemotherapy

• DOI: 10.3389/fimmu.2022.951137
• Publication Date: 2022-08-05T20:38:05Z
• Authors: Qihang Yuan; Dawei Deng; Chen Pan; Jie Ren; Tianfu Wei; Zeming Wu; Biao Zhang; Shuang Li; Peiyuan Yin; Dong Shang
• Keywords: Metabolome; Metabolic pathway

Currently available prognostic tools and focused therapeutic methods result in unsatisfactory treatment of gastric cancer (GC). A deeper understanding human epidermal growth factor receptor 2 (HER2)-coexpressed metabolic pathways may offer novel insights into tumour-intrinsic precision medicine.The integrated multi-omics strategies (including transcriptomics, proteomics metabolomics) were applied to develop a classifier for cancer. We TCGA-STAD cohort (375 GC samples 56753 genes) TCPA-STAD (392 218 proteins), rated them as transcriptomics data, resepectively. 224 matched blood patients healthy individuals collected carry out untargeted metabolomics analysis.In this study, pan-cancer analysis highlighted the crucial role ERBB2 immune microenvironment remodelling. In addition, landscape indicated that alanine, aspartate glutamate (AAG) metabolism was significantly associated with prevalence progression GC. Weighted metabolite correlation network revealed glycolysis/gluconeogenesis (GG) AAG served HER2-coexpressed pathways. Consensus clustering used stratify four subtypes different characteristics (i.e. quiescent, GG, mixed subtypes). The GG subtype characterised by lower level expression, higher proportion inflammatory phenotype worst prognosis. However, contradictory features found best be highly sensitive chemotherapy, whereas quiescent more likely benefit from immunotherapy.Transcriptomic proteomic analyses close association HER-2 status Metabolomics co-expressed relationship between metabolisms HER2 strategy study facilitate development tailored approach therapy.