胃癌（GC）的治疗仍然存在挑战，因其高发病率和不良预后。胶原蛋白Vα2（COL5A2）在多种癌症中增加，然而其对GC的预后和免疫作用尚不清楚。我们使用The Cancer Genome Atlas（TCGA）和Gene Expression Omnibus（GEO）数据集，下载了转录组分析（TCGA-STAD；GSE84437）、单细胞RNA测序（scRNA-seq）数据（GSE167297）和临床信息。分析了COL5A2表达及其与临床病理因素的关系。我们进行了生存分析和Cox回归分析，评估了GC的预后和独立因素。还进行了共表达分析。为了确定潜在机制，我们进行了差异表达基因（DEGs）和功能富集分析。进一步探索了COL5A2表达与免疫细胞浸润水平及免疫浸润基因标记集的相关性。此外，我们还分析了COL5A2表达与免疫检查点分子的关联性。此外，还研究了COL5A2表达与免疫治疗敏感性之间的关系。GC中COL5A2表达升高。更重要的是，单细胞RNA测序分析揭示了COL5A2表达具有空间梯度。升高的COL5A2与较差的总生存相关。在GC中发现COL5A2过表达与年龄、T分类和临床分期有显著相关性。Cox回归分析显示COL5A2是不良预后的独立因素。COL5A2的共表达基因与肿瘤分期或不良生存相关。富集分析显示DEGs主要与细胞外基质（ECM）相关的过程、PI3K-AKT信号通路和黏附斑相关。GSEA分析显示COL5A2与肿瘤进展相关的通路相关。同时，COL5A2表达与肿瘤浸润免疫细胞相关。此外，免疫表型分析（IPS）和PRJEB25780队列显示低COL5A2表达的患者对免疫疗法高度敏感。COL5A2可能作为GC预后和免疫浸润的预测生物标志物，并且可能提供治疗干预策略。©2023 BioMed Central Ltd.，Springer Nature的一部分。

There is still a therapeutic challenge in treating gastric cancer (GC) due to its high incidence and poor prognosis. Collagen type V alpha 2 (COL5A2) is increased in various cancers, yet it remains unclear how it contributes to the prognosis and immunity of GC.The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to download transcriptome profiling (TCGA-STAD; GSE84437), single-cell RNA sequencing (scRNA-seq) data (GSE167297) and clinical information. COL5A2 expression and its relationship with clinicopathological factors were analyzed. We conducted survival analysis and Cox regression analysis to evaluate the prognosis and independent factors of GC. Co-expressed analysis was also performed. To identify the underlying mechanism, we conducted analyses of differentially expressed genes (DEGs) and functional enrichment. The correlations between COL5A2 expression and immune cell infiltration levels and immune infiltrate gene marker sets were further explored. Additionally, we analyzed the association of COL5A2 expression with immunological checkpoint molecules. Furthermore, the relationship between COL5A2 expression and immunotherapy sensitivity was also investigated.COL5A2 expression was elevated in GC. More than this, the scRNA-seq analysis revealed that COL5A2 expression had a spatial gradient. The upregulated COL5A2 was associated with worse overall survival. A significant correlation was found between COL5A2 overexpression and age, T classification and clinical stage in GC. COL5A2 was found to be an independent factor for the unfortunate outcome in Cox regression analysis. The co-expressed genes of COL5A2 were associated with tumor stage or poor survival. Enrichment analysis revealed that the DEGs were mainly associated with extracellular matrix (ECM)-related processes, PI3K-AKT signaling pathway, and focal adhesion. GSEA analyses revealed that COL5A2 was associated with tumor progression-related pathways. Meanwhile, COL5A2 expression was correlated with tumor-infiltrating immune cells. Moreover, immunophenoscore (IPS) analysis and PRJEB25780 cohorts showed that patients with low COL5A2 expression were highly sensitive to immunotherapy.COL5A2 might act as a prognostic biomarker of GC prognosis and immune infiltration and may provide a therapeutic intervention strategy.© 2023. BioMed Central Ltd., part of Springer Nature.