基于生物信息学分析含锌指CCCH结构域蛋白13在胃癌中的作用

The role of zinc finger CCCH-type containing 13 in gastric cancer based on bioinformatics analysis

  • 摘要:
    目的 基于生物信息学技术探讨含锌指CCCH结构域蛋白13(ZC3H13)在胃癌组织中的表达水平、临床病理分期、预后生存、免疫浸润程度、相关性分析、蛋白间相互作用及富集分析。
    方法 应用UALCAN、基于基因表达谱交互式分析平台(GEPIA)数据库比较ZC3H13在正常胃组织和胃癌组织中表达差异。使用Kaplan-Meier Plotter网站和GEPIA数据库评估胃癌组织中ZC3H13的表达水平与患者生存预后的相关性。采用肿瘤浸润免疫细胞分析(TIMER)数据库探讨ZC3H13表达与胃癌免疫浸润水平的关系。利用Linkedomics数据库筛选在胃癌组织中与ZC3H13显著共表达的基因。使用STRING网站得出ZC3H13与胃癌共同靶点基因的蛋白质相互作用网络,并开展基于基因本体论(GO)和京都基因与基因组百科全书(KEGG)的富集分析。
    结果 与正常胃组织相比, ZC3H13在胃癌组织中的表达升高,且其高表达与患者年龄、种族、组织亚型等密切相关。ZC3H13高表达与低表达的胃癌患者在总生存率和无进展生存率方面差异无统计学意义(P>0.05)。免疫分析发现,在胃癌组织中, ZC3H13与CD8+T细胞、巨噬细胞、中性粒细胞及树突状细胞的肿瘤浸润密度存在显著负相关(P<0.05)。相关性分析显示, ZC3H13与胃癌组织中DAKDDK1BCL7C等基因的表达呈正相关,与FAM10A4SLC6A7TAC1等基因的表达呈负相关(P<0.05)。蛋白互作网络显示,胃癌组织中,与ZC3H13产生相互作用的蛋白包括VIRMA、WTAP、METTL3、METTL14、RBM15等。富集分析显示,在胃癌组织中,差异基因主要富集于RNA聚合酶、核苷酸切除修复、甲状腺激素信号通路等。
    结论 ZC3H13在胃癌组织中呈高表达,其高表达与临床病理分期、患者生存时间、免疫细胞浸润程度有关,且ZC3H13可能通过与VIRMA、METTL3等关键分子的协同作用参与胃癌的发生发展,提示ZC3H13或可作为胃癌预后的潜在生物标志物和治疗靶点。

     

    Abstract:
    Objective To explore the expression level of zinc finger CCCH-type containing 13 (ZC3H13) in gastric cancer based on bioinformatics techniques, along with clinicopathological staging, prognostic survival, immune infiltration, correlation analysis, protein-protein interactions, and enrichment analysis.
    Methods Using the UALCAN database and the Gene Expression Profiling Interactive Analysis (GEPIA) databases, the expression differences of ZC3H13 between normal gastric tissues and gastric cancer tissues, as well as the significance of clinical pathological data were compared. The correlation between ZC3H13 expression levels in gastric cancer tissues and patient survival prognosis was assessed using univariate survival analysis through the Kaplan-Meier Plotter website and the GEPIA database. The relationship between ZC3H13 expression and immune infiltration levels in gastric cancer was explored using the Tumor Immune Estimation Resource (TIMER) database. Co-expression genes significantly correlated with ZC3H13 expression in gastric cancer were identified through the Linkedomics database. The protein-protein interaction network of ZC3H13 and its common target genes in gastric cancer was constructed using the STRING website, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses.
    Results Compared to normal gastric tissues, ZC3H13 was significantly upregulated in gastric cancer, and its high expression was closely associated with patient age, ethnicity, tissue subtype, and other factors. Patients with high ZC3H13 expression showed no statistically significant difference in overall survival (OS) or progression-free survival (PFS) time compared to patients with low expression (P>0.05). Immune analysis revealed a significant negative correlation between ZC3H13 expression and the infiltration density of CD8+ T cells, macrophages, neutrophils, and dendritic immune cells in gastric cancer (P < 0.05). Correlation analysis showed that ZC3H13 expression in gastric cancer was significantly positively correlated with the gene expression of DAK, DDK1, and BCL7C, and negatively correlated with the expression of FAM10A4, SLC6A7, and TAC1 (P < 0.05). The protein interaction network indicated that proteins interacting with ZC3H13 in gastric cancer included VIRMA, WTAP, METTL3, METTL14, RBM15, and others. Enrichment analysis revealed that differentially expressed genes in gastric cancer were mainly enriched in RNA polymerase, nucleotide excision repair, thyroid hormone signaling pathway, and other pathways.
    Conclusion ZC3H13 is overexpressed in gastric cancer, and its elevated expression is linked to the clinicopathological stage, patient survival time, and immune cell infiltration levels. Additionally, ZC3H13 may participate in the initiation and progression of gastric cancer through interactions with key molecules such as VIRMA and METTL3. These findings suggest that ZC3H13 could serve as a potential biomarker and therapeutic target for gastric cancer prognosis.

     

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