[关键词]
[摘要]
目的:采用生物信息学方法分析E3泛素连接酶(HECW2)在胃腺癌组织中的表达及其临床意义,为寻找胃腺癌诊断和预后生物标志物提供新的线索。方法:用R语言分析HECW2在泛癌中的表达及其与泛癌预后的关系。借助UCSC Xena、HPA、Kaplan-Meier Plotter等数据库分析HECW2在胃腺癌组织中的表达及其与临床病理特征之间的关系。采用WB法检测中国人胃腺癌组织及其癌旁组织中HECW2蛋白水平以验证数据库中的分析结果。借助TIMER和Cibersort数据库分析HECW2与胃腺癌免疫浸润的关系。通过LinkedOmics数据库对胃腺癌中HECW2进行GO功能分析和KEGG信号通路富集分析及相关性基因分析。结果:生物信息学分析结果表明,33种不同类型肿瘤中,包括胃腺癌在内的12种肿瘤中HECW2呈显著高表达(均P<0.05),WB 法结果显示,中国人胃腺癌组织中 HECW2 也呈显著高表达(P<0.05)。HECW2 表达水平越高,胃腺癌患者 OS 越短,包括CD4+T细胞、巨噬细胞、中性粒细胞和树突状细胞在内的免疫细胞浸润丰度越高(均P?0.01)。此外,HECW2相关信号通路主要富集于细胞外基质受体相互作用、黏着斑、细胞黏附和氧化磷酸化等生理病理过程(均P?0.01)。结论:HECW2在胃腺癌组织中呈显著高表达且其与胃腺癌预后不良和免疫细胞浸润密切相关,有成为胃腺癌预后标志物和治疗靶点的潜力。
[Key word]
[Abstract]
Objective: To analyze the expression and clinical significance of E3 ubiquitin ligase (HECW2) in gastric adenocarcinoma using a bioinformatics approach to provide new clues for finding diagnostic and prognostic biomarkers for gastric adenocarcinoma.Methods: The expression of HECW2 in pan-cancer and its relationship with the prognosis of pan-cancer were analyzed by R language.The expression of HECW2 in gastric adenocarcinoma tissues and its relationship with clinicopathological features were analyzed with the help of UCSC Xena, HPA, and Kaplan-Meier Plotter databases. The WB method was used to detect HECW2 protein levels in Chinese gastric adenocarcinoma tissues and their paraneoplastic tissues to verify the analysis results in the database. The relationship between HECW2 and immune infiltration of gastric adenocarcinoma was analyzed with the help of TIMER and Cibersort databases.GO functional analysis and KEGG signaling pathway enrichment analysis and correlation gene analysis were performed for HECW2 in gastric adenocarcinoma by LinkedOmics database. Results: The results of raw signal analysis showed that HECW2 was significantly highly expressed in 12 tumors including gastric adenocarcinoma among 33 different types of tumors (all P<0.05), and the results of WB method showed that HECW2 was also significantly highly expressed in Chinese gastric adenocarcinoma tissues (P<0.05). Higher HECW2 expression level was associated with shorter OS and higher abundance of infiltration of immune cells including CD4+T cells, macrophages, neutrophils and dendritic cells in gastric adenocarcinoma patients (all P?0.01). In addition, HECW2-associated signaling pathways were mainly enriched in extracellular matrix receptor interactions, adherent spots, cell adhesion and oxidative phosphorylation (all P?0.01). Conclusion: HECW2 is significantly overexpressed in gastric adenocarcinoma tissues and is closely related to the poor prognosis and immune invasion of gastric adenocarcinoma, and has great potential as a prognostic biomarker and target therapy for gastric adenocarcinoma.
[中图分类号]
[基金项目]
陕西省自然科学基础研究计划资助项目(No.2022JQ-907);陕西省高校科协青年人才托举计划项目(No.20210309);2021年国家级 大学生创新创业训练计划项目(No.202110719015)