Objective: Gastric carcinoma (GC) is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related deaths globally. The tumor microenvironment plays a significant role in the pathogenesis, prognosis, and response to immunotherapy. However, the immune-related molecular mechanisms underlying GC remain elusive. Bioinformatics analysis of the gene expression of GC and paracancerous healthy tissues from the same patient was performed to identify the key genes and signaling pathways, as well as their correlation to the infiltration of the tumor microenvironment (TME) by various immune cells related to GC development. Methods: We employed GSE19826, a gene expression profile from the Gene Expression Omnibus (GEO), for our analysis. Functional enrichment analysis of Differentially Expressed Genes (DEGs) was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database. Results: Cytoscape software facilitated the identification of nine hub DEGs, namely,FN1,COL1A1,COL1A2,THBS2,COL3A1,COL5A1,APOE,SPP1, andBGN.Various network analysis algorithms were applied to determine their high connectivity. Among these hub genes,FN1,COL1A2,THBS2,COL3A1,COL5A1, andBGNwere found to be associated with a poor prognosis for GC patients. Subsequent analysis using the TIMER database revealed the infiltration status of the TME concerning the overexpression of these six genes. Specifically, the abovementioned genes demonstrated direct correlations with cancer-associated fibroblasts, M1 and M2 macrophages, myeloid-derived suppressor cells, and activated dendritic cells. Conclusion: Our findings suggest that the identified hub genes, particularlyBGN,FN1,COL1A2,THBS2,COL3A1, andCOL5A1, play crucial roles in GC prognosis and TME cell infiltration. This comprehensive analysis enhances our understanding of the molecular mechanisms underlying GC development and may contribute to the identification of potential therapeutic targets and prognostic markers for GC patients.
目的：胃癌是全球第五大常见确诊癌症及第三大癌症相关死亡原因。肿瘤微环境在其发病机制、预后及免疫治疗反应中具有重要作用，然而胃癌相关的免疫分子机制尚未明确。本研究通过对同一患者胃癌组织与癌旁正常组织的基因表达进行生物信息学分析，旨在识别关键基因及信号通路，并探究其与胃癌发展中各类免疫细胞浸润肿瘤微环境的相关性。方法：采用基因表达综合数据库中的GSE19826基因表达谱进行分析，通过基因本体论和京都基因与基因组百科全书数据库对差异表达基因进行功能富集分析。结果：利用Cytoscape软件鉴定出九个核心差异表达基因：FN1、COL1A1、COL1A2、THBS2、COL3A1、COL5A1、APOE、SPP1和BGN。通过多种网络分析算法确认这些基因具有高度连接性，其中FN1、COL1A2、THBS2、COL3A1、COL5A1和BGN与胃癌患者不良预后相关。基于TIMER数据库的后续分析揭示了这六个基因过表达与肿瘤微环境浸润状态的关系，具体表现为上述基因与癌症相关成纤维细胞、M1/M2型巨噬细胞、髓源性抑制细胞及活化树突状细胞呈直接正相关。结论：本研究发现的核心基因，特别是BGN、FN1、COL1A2、THBS2、COL3A1和COL5A1，在胃癌预后及肿瘤微环境细胞浸润中发挥关键作用。该综合分析深化了对胃癌发展分子机制的理解，可能为胃癌患者潜在治疗靶点与预后标志物的识别提供重要依据。
肿瘤(癌症)患者之家