| 陈艳,毕磊,高波.锌指蛋白 32在泛癌中的表达、预后意义及其与肝癌免疫微环境的相关性[J].安徽医药,2025,29(7):1328-1335. |
| 锌指蛋白 32在泛癌中的表达、预后意义及其与肝癌免疫微环境的相关性 |
| Expression and prognostic significance of zinc finger protein 32 in pan-cancer and its correlation with immune microenvironment of hepatocellular carcinoma |
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| DOI：10.3969/j.issn.1009-6469.2025.07.013 |
| 中文关键词: 锌指蛋白 泛癌 预后 肝癌 免疫浸润 肿瘤微环境 |
| 英文关键词: Zinc finger protein Pan-cancer Prognosis Hepatocellular carcinoma Immune infiltrating cells Tumor microen-vironment |
| 基金项目:国家自然科学基金项目( 82160582)；云南省科技厅基础研究计划面上项目( 202201AT070003)；云南省高层次卫生健康技术人才培养项目( H-2024019)；大理市科研基金项目( 2021KBG036) |
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| 中文摘要: |
| 目的基于多数据库分析锌指蛋白 32(zinc finger protein 32，ZNF32)在泛癌中的表达和预后价值，探究 ZNF32与肿瘤微环境的关系。方法从美国国家生物技术信息中心( NCBI)和人类蛋白质图谱( HPA)数据库分析 ZNF32的基因定位、正常组织中的表达及肿瘤细胞中的表达定位；利用 TIMER2.0、Sangerbox、TNM plot和 UALCAN数据库分析 ZNF32在 33种肿瘤中的表达差异、临床特征和预后价值；利用 cBioPortal数据库分析 ZNF32基因变异特征；利用 TIMER2.0和 TISIDB数据库分析 ZNF32与免疫细胞浸润及免疫调节基因的相关性；利用 GENEMANIA数据库构建 ZNF32蛋白互作网络；利用 UALCAN数据库获取肿瘤中 ZNF32的相关基因，进行基因本体以及京都基因和基因组数据库通路富集分析。结果正常组织中的 ZNF32表达特异性较低， ZNF32在多种肿瘤中表达高于正常组织。 ZNF32表达与肾上腺皮质癌、乳腺癌、头颈鳞状细胞癌、肝癌、葡萄膜黑色素瘤分期呈正相关，与头颈鳞状细胞癌、肝癌和胃癌分级呈正相关(均 P<0.05)。 ZNF32高表达对于急性髓细胞样白血病、肝癌、乳腺癌和肾上腺皮质癌病人的预后是一个独立危险因素，且与 ZNF32低表达肝癌病人相比， ZNF32高表达肝癌病人的总体生存期、疾病特异性生存期、无疾病间隔期、无进展间隔期均显著短(均 P<0.05)。肿瘤中 ZNF32基因突变也预示着更差的预后。肝癌中 ZNF32表达与多种免疫细胞浸润、免疫检查点基因、趋化因子及其受体密切相关(均 P<0.05)。 ZNF32与 RELL2、TLL2、 ZBTB22等基因存在互作关系，且可能通过参与 Hippo信号转导、信使 RNA(messenger RNA，mRNA)监测、泛素介导的蛋白降解、细胞周期、范科尼贫血等信号通路调控肝癌的发生发展。结论全面的泛癌分析确定 ZNF32可作为肿瘤诊断和不良预后的生物标志物，与肿瘤免疫浸润相关，为 ZNF32作为未来肿瘤免疫治疗的关键靶点提供了新的见解。 |
| 英文摘要: |
| Objective To analyze the expressions of zinc finger protein 32 (ZNF32) in pan-cancer and its role in patients' prognosisbased on data from multiple databases, and to explore the relationship between ZNF32 and the tumor immune microenvironment.Meth. ods ZNF32 gene mapping, ZNF32 expression levels and location in the pan-cancer tissues and normal tissues were obtained from Na-tional Center for Biotechnology Information (NCBI) and The Human Protein Atlas (HPA) database. The TIMER 2.0, Sangerbox, TNMplot and UALCAN databases were used to analyze the expression differences, clinical characteristics and prognostic value of ZNF32 in33 tumors. The gene variation features of ZNF32 were analyzed using cBioPortal database. Correlations of ZNF32 expression level withimmune cell infiltration and immunomodulatory factors were analyzed by TIMER 2.0 and TISIDB. The protein-protein interaction net-works were constructed by GENEMANIA database. ZNF32 related genes were obtained through UALCAN database, and Gene Ontolo-gy, Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the differential genes.Results The expressionspecificity of ZNF32 in normal tissues was low and ZNF32 was highly expressed in multiple tumors than normal tissue. There was a pos-itive correlation between ZNF32 expression and cancer staging in adrenocortical carcinoma, breast invasive carcinoma, head and necksquamous cell carcinoma, liver hepatocellular carcinoma and uveal melanoma, and ZNF32 was also positively correlated with tumorgrading in head and neck squamous cell carcinoma, liver hepatocellular carcinoma and stomach adenocarcinoma (all P<0.05). High ex-pression of ZNF32 was an independent risk factor for the progosis of patients with acute myeloid leukemia, liver hepatocellular carcino-ma, breast invasive carcinoma and adrenocortical carcinoma. Compared with the liver hepatocellular carcinoma patients with low ex-pression of ZNF32, liver hepatocellular carcinoma patients with high expression of ZNF32 had shorter overall survival, disease-specific survival, disease-free interval, and progression-free interval (all P<0.05). Mutations of ZNF32 gene in tumors also predicted a worseprognosis. ZNF32 expression was closely associated with various immune cell infiltration, immune checkpoint genes, chemokines andchemokine receptors in liver hepatocellular carcinoma (all P<0.05). ZNF32 interacted with RELL2, TLL2, ZBTB22 and other genes,and ZNF32 might regulate the occurrence and development of liver hepatocellular carcinoma by participating in Hippo signaling, mes-senger RNA (mRNA) surveillance pathway, ubiquitin-mediated proteolysis, cell cycle, Fanconi anemia pathway and other signaling pathways.Conclusion Comprehensive pan-cancer analysis confirmed that ZNF32 is a biomarker for tumor diagnosis and poor cancerprognosis, and that it is associated with tumor immune-infiltration, providing new insights into ZNF32 as a key target for tumor immuno-therapy in the future. |
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