[关键词]
[摘要]
[摘 要] 目的:筛选炎症性肠病(IBD)和结直肠癌(CRC)的潜在共病基因,探讨关键基因去整合素-金属蛋白酶8(ADAM8)与 IBD及CRC发生发展的关系及其潜在机制。方法:基于从GEO数据库和TCGA数据库下载IBD及CRC患者的转录组数据及对 应临床资料,通过差异分析、预后基因筛选及交集分析鉴定同致共病基因。用多个数据集分析和验证关键基因ADAM8在IBD及 CRC中的表达特征及其与临床病理指标的关系。生存分析探究ADAM8在CRC中的预后价值。功能和通路富集分析探究 ADAM8影响CRC进展的潜在机制,进一步用肿瘤微环境算法评估ADAM8与肿瘤微环境的关系。用免疫组化(IHC)法检测中 国人CRC组织中的表达验证数据库数据。结果: ADAM8为IBD和CRC的潜在关键共病基因。ADAM8在IBD和CRC组织中 均呈高表达(均P < 0.01),且其高表达提示疾病病理进展(P < 0.01)。高表达ADAM8的CRC患者总生存期(OS)更短(P < 0.05 或P < 0.01)。ADAM8在中国人CRC组中也呈高表达(P < 0.01)。免疫细胞迁移、细胞因子产生及免疫受体相互作用等通路与 ADAM8表达密切关联,ADAM8表达与中性粒细胞、巨噬细胞等免疫细胞浸润水平呈正相关(P < 0.01或P < 0.001)。结论: ADAM8在IBD和CRC组织中呈高表达,与患者预后、疾病进展及免疫细胞浸润密切关联,有望成为2种疾病的共同干预靶点。
[Key word]
[Abstract]
[Abstract] Objective: To screen potential comorbid genes shared between inflammatory bowel disease (IBD) and colorectal cancer (CRC), and to explore the relationship between the key gene a disintegrin and metalloprotease 8 (ADAM8) and the pathogenesis of IBD and CRC, as well as the underlying mechanisms. Methods: Transcriptomic data and corresponding clinical information for IBD and CRC were downloaded from the GEO database and TCGA database. Differential expression analysis, prognostic gene screening, and intersection analysis were performed to identify shared genes. Multiple datasets were used to analyze and validate the expression patterns of ADAM8 in IBD and CRC and its correlation with clinicopathological features. Survival analysis was conducted to evaluate the prognostic value of ADAM8 in CRC. Functional and pathway enrichment analyses were conducted to explore the potential mechanisms by which ADAM8 influences CRC progression. The correlation between ADAM8 and tumor microenvironment components was further assessed using tumor microenvironmental algorithms. The database data was validated by detecting the expression in Chinese CRC tissues using immunohistochemistry (IHC). Results: ADAM8 was identified as a potential shared comorbidity gene in IBD and CRC. ADAM8 was significantly upregulated in both IBD and CRC tissues (all P < 0.01), and its high expression was associated with disease progression (P < 0.01). CRC patients with high ADAM8 expression had shorter overall survival (OS) (P < 0.05 or P < 0.01). ADAM8 was also significantly highly expressed in Chinese CRC tissues (P < 0.01). Pathway analysis revealed that ADAM8 expression was closely linked to immune cell migration, cytokine production, and immune receptor interactions. Additionally, ADAM8 expression positively correlated with immune cell infiltration, including neutrophils and macrophages (P < 0.01 or P < 0.001). Conclusion: ADAM8 is highly expressed in IBD and CRC tissues and is closely associated with patient prognosis, disease progression, and immune cell infiltration. It holds promise as a common therapeutic target for both diseases.
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[基金项目]
海南省自然科学基金青年基金项目(No.820QN419)