Figure 1 GSE13911.xlsx

COL12A1, a collagen type XII alpha 1 chain, has an instrumental role in the extracellular matrix (ECM), but its effect on gastric cancer (GC) and clinical significance remain unclear. In this study, co-expressed differentially expressed genes (co-DEGs) were identified using Venn diagrams based on datasets from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) for gastric cancer RNA sequencing. Intersections between co-DEGs and TCGA prognosis-related genes were used to pinpoint genes that were differentially associated with prognosis. COL12A1 emerged as a key candidate gene. We analyzed COL12A1 expression in human GC tissues and explored its association with various clinicopathological parameters. Survival analysis, including overall survival (OS) and disease-free survival (DFS), was conducted using TCGA data, and a prognostic nomogram was constructed. The relative protein-encoding gene expression was assessed via immunohistochemistry (IHC) analysis of four downloaded datasets, along with PCR experiments. COL12A1-related DEGs were further identified using the LinkedOmics database, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Multiple databases were analysed for the relationship between COL12A1 and methylation. Immune cell infiltration was evaluated through CIBERSORT and TIMER databases, revealing a strong correlation between COL12A1 expression and immune cell presence in the tumor microenvironment. Single-cell expression analysis using TISCH provided further insights into the cellular context of COL12A1 expression. TISCH was used to analyse the single-cell expression of COL12A1. Finally, this work examined the correlation of COL12A1 with drug sensitivity via the RNAactDrug database. COL12A1 overexpression in gastric cancer was detected and found to be closely related to clinicopathological features. GO/KEGG functional enrichment analysis revealed that COL12A1 was associated with pathways such as extracellular structure organization, extracellular matrix organization and the collagen-containing extracellular matrix. Analysis of several databases revealed that COL12A1 was associated with gene mutation and methylation. Additionally, as revealed by CIBERSORT profiling and TIMER database analysis, COL12A1 expression is related to immune cell infiltration. Correlation analysis via the RNAactDrug website revealed that COL12A1 is associated with drug sensitivity. In conclusion, COL12A1 is significantly overexpressed in gastric cancer and is associated with tumor progression, immune infiltration, and drug sensitivity. These findings suggest that COL12A1 may serve as a potential diagnostic and therapeutic biomarker for gastric cancer.

COL12A1（XII型胶原α1链，collagen type XII alpha 1 chain）在细胞外基质（extracellular matrix，ECM）中发挥关键作用，但其在胃癌（gastric cancer，GC）中的功能效应及临床意义仍未明确。本研究基于癌症基因组图谱（The Cancer Genome Atlas，TCGA）与基因表达综合数据库（Gene Expression Omnibus，GEO）的胃癌RNA测序数据集，通过韦恩图筛选鉴定共表达差异表达基因（co-expressed differentially expressed genes，co-DEGs）。将共表达差异基因与TCGA预后相关基因取交集，以锁定与预后显著相关的差异基因，最终筛选出COL12A1作为核心候选基因。随后，本研究分析了COL12A1在人胃癌组织中的表达水平，并探讨其与各类临床病理参数的关联。利用TCGA数据开展总生存期（overall survival，OS）与无病生存期（disease-free survival，DFS）相关的生存分析，并构建预后列线图。通过下载的4个数据集的免疫组化（immunohistochemistry，IHC）分析及PCR实验，评估其编码蛋白基因的相对表达量。使用LinkedOmics数据库进一步筛选COL12A1相关的差异表达基因，随后进行基因本体（Gene Ontology，GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）富集分析。通过多个数据库分析COL12A1与甲基化的相关性。通过CIBERSORT与TIMER数据库评估肿瘤微环境中的免疫细胞浸润情况，发现COL12A1表达与免疫细胞浸润程度显著相关。使用TISCH数据库开展单细胞表达分析，进一步揭示COL12A1表达的细胞分布特征。最后，本研究通过RNAactDrug数据库分析COL12A1与药物敏感性的相关性。研究结果显示，胃癌组织中COL12A1呈高表达状态，且与临床病理特征密切相关。GO/KEGG功能富集分析表明，COL12A1参与细胞外结构组织、细胞外基质组织及含胶原细胞外基质等生物学通路。多数据库分析证实，COL12A1与基因突变及甲基化水平相关。此外，CIBERSORT分析与TIMER数据库结果均显示，COL12A1表达与免疫细胞浸润呈显著正相关。通过RNAactDrug网站的相关性分析发现，COL12A1与多种药物的敏感性相关。综上，COL12A1在胃癌中显著高表达，且与肿瘤进展、免疫浸润及药物敏感性密切相关。上述研究结果提示，COL12A1有望成为胃癌潜在的诊断与治疗生物标志物。