胃腺癌(GAC)是世界上最致命的恶性肿瘤之一。已经确认GAC的发生和进展与分子变化有关。然而，GAC的发病机制仍不清楚。本研究对6对GAC肿瘤组织和相邻正常组织进行了基因测序，并从TCGA数据库中收集了GAC基因表达谱数据。对这些数据的分析显示有465个差异表达基因(DEGs)，其中246个上调，219个下调。基因组学数据库(Kyoto Encyclopedia of Genes and Genomes (KEGG))通路分析显示DEGs在细胞外基质-受体相互作用通路、蛋白质消化和吸收通路以及胃酸分泌通路中明显富集。通过生存分析，从蛋白质相互作用网络(PPI)筛选出了6个与GAC预后不良相关的关键基因(MATN3，COL1A1，COL5A2，P4HA3，SERPINE1和VCAN)，其中P4HA3和MATN3极少被报道与GAC有关。我们进一步在GAC细胞株SGC-7901中通过逆转录-实时荧光定量PCR(RT-qPCR)，MTT，流式细胞术，克隆形成，划痕愈合，Transwell和western blot实验分析了P4HA3在GAC细胞中的功能。我们发现与正常对照细胞相比，SGC-7901细胞系中P4HA3上调。通过失功能试验的结果表明，P4HA3显著增强了GAC细胞的增殖和迁移能力。本研究为选择GAC预后标记和治疗靶点提供了新的基础。©2023。作者，独家许可 Springer Science+Business Media，LLC，Springer Nature部分拥有版权。

Gastric adenocarcinoma (GAC) is one of the world's most lethal malignant tumors. It has been established that the occurrence and progression of GAC are linked to molecular changes. However, the pathogenesis mechanism of GAC remains unclear. In this study, we sequenced 6 pairs of GAC tumor tissues and adjacent normal tissues and collected GAC gene expression profile data from the TCGA database. Analysis of this data revealed 465 differentially expressed genes (DEGs), of which 246 were upregulated and 219 were downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that DEGs were observably enriched in ECM-receptor interaction, protein digestion and absorption, and gastric acid secretion pathways. Six key genes (MATN3, COL1A1, COL5A2, P4HA3, SERPINE1 and VCAN) associated with poor GAC prognosis were screened from the protein‒protein interaction (PPI) network by survival analysis, and P4HA3 and MATN3 have rarely been reported to be associated with GAC. We further analyzed the function of P4HA3 in the GAC cell line SGC-7901 by RT‒qPCR, MTT, flow cytometry, colony formation, wound healing, Transwell and western blot assays. We found that P4HA3 was upregulated in the SGC-7901 cell line versus normal control cells. The outcomes of the loss-of-function assay illustrated that P4HA3 significantly enhanced the ability of GAC cells to proliferate and migrate. This study provides a new basis for the selection of prognostic markers and therapeutic targets for GAC.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.