Gastric cancer is one of the most common cancers and ranks third in cancer-related deaths across globe. Cancer cells are known to take advantage of the altered metabolic processes to sustain their survival, proliferation, and cancer progression. In this investigation, we explored the available genome-wide expression profiles of few hundreds of gastric tumors and non-cancerous gastric tissues and analyzed in the context of metabolic pathways. Gastric tumors were investigated for the metabolic processes related to glucose metabolism, glucose transport, glutamine metabolism, and fatty acid metabolism, by metabolic pathway-focused gene set enrichment analysis. Notably, all glucose metabolism and glutamine metabolism-related gene sets were found enriched in intestinal subtype gastric tumors. On the other hand, the gene sets related to glucose transport and glucan (glycan) metabolisms are enriched in diffuse subtype gastric tumors. Strikingly, fatty acid metabolisms, fatty acid transport, and fat differentiation-related signatures are also highly activated in diffuse subtype gastric tumors. Exploration of the recently established metabolome profile of the massive panel of cell lines also revealed the metabolites of glucose and fatty acid metabolic pathways to show the differing abundance across gastric cancer subtypes. The subtype-specific metabolic rewiring and the existence of two distinct metabolic dysregulations involving glucose and fatty acid metabolism in gastric cancer subtypes have been identified. The identified differing metabolic dysregulations would pave way for the development of targeted therapeutic strategies for the gastric cancer subtypes.

胃癌是最常见的癌症之一，在全球与癌症相关的死亡中排名第三。已知癌细胞利用改变的代谢过程来维持其生存，增殖和癌症进展。在这项调查中，我们探索了数百种胃肿瘤和非癌性胃组织的可用全基因组表达谱，并在代谢途径的背景下进行了分析。通过以代谢途径为重点的基因集富集分析，研究了胃肿瘤中与葡萄糖代谢，葡萄糖转运，谷氨酰胺代谢和脂肪酸代谢有关的代谢过程。值得注意的是，发现所有葡萄糖代谢和谷氨酰胺代谢相关的基因组都富含肠道亚型胃肿瘤。另一方面，与葡萄糖转运和葡聚糖（聚糖）代谢有关的基因组富含弥散性亚型胃肿瘤。令人惊讶的是，在弥散性亚型胃肿瘤中，脂肪酸代谢，脂肪酸运输和与脂肪分化相关的信号也被高度激活。对大量细胞系新近建立的代谢组谱的探索还揭示了葡萄糖和脂肪酸代谢途径的代谢物，显示了跨胃癌亚型的不同丰度。已经鉴定出亚型特异性代谢重新连接以及胃癌亚型中存在涉及葡萄糖和脂肪酸代谢的两种不同的代谢失调。