HERC6可作为肾透明细胞肾细胞癌的预后标志物和潜在治疗靶点:基于生信分析和实验验证  

HERC6 can serve as a prognostic biomarker and a potential therapeutic target for kidney clear cell renal cell carcinoma:based on bioinformatics analysis and experimental verification

作　　者：移昕诚 贾宗铭 孔颖 龚东魁 黄玉华[1] YI Xincheng;JIA Zongming;KONG Ying;GONG Dongkui;HUANG Yuhua(Department of Urology,the First Affiliated Hospital of Soochow University,Jiangsu 215000)

机构地区：[1]苏州大学附属第一医院泌尿外科,江苏215000

出　　处：《南通大学学报(医学版)》2025年第1期14-21,共8页Journal of Nantong University(Medical sciences)

基　　金：国家自然科学基金资助项目(82002685)。

摘　　要：目的:探讨E3泛素连接酶HERC6(hect and RLD domain containing E3 ubiquitin protein ligase family member 6)是否可作为肾透明细胞肾细胞癌(kidney clear cell renal cell carcinoma,KIRC)预后的标志物和治疗的靶点。方法:用癌症基因图谱(the cancer genome atlas,TCGA)数据库分析在KIRC中HERC6的表达。运用UALCAN数据库评估HERC6与KIRC的临床相关性。进行单因素Cox回归分析,构建HERC6在KIRC的预后模型。探究HERC6表达与免疫细胞浸润、免疫相关功能以及免疫检查点之间的关联性。通过药物敏感性分析探究HERC6作为靶向治疗新靶点的可能。最后,开展5-乙炔基-2'脱氧尿嘧啶掺入测定(5-ethynyl-2'-deoxyuridine incorporation assay,EdU)实验、划痕实验和Transwell实验,以验证HERC6在KIRC发生、进展中的作用。结果:HERC6在KIRC中的表达与正常肾组织相比明显减低(P<0.001)。HERC6低表达的患者预后较差,临床病理特征也更不理想。功能富集分析显示,HERC6主要参与免疫反应、脂质代谢等生物学过程,进而介导KIRC的发展。免疫相关分析表明,HERC6是KIRC免疫治疗的潜在靶点。在KIRC细胞中过表达HERC6进行体外实验,发现其增殖、迁移和侵袭能力被抑制。结论:HERC6可作为KIRC预后标志物和治疗靶点。Objective:To explore whether the E3 ubiquitin-ligase hect and RLD domain containing E3 ubiquitin protein ligase family member 6(HERC6)can serve as a prognostic marker and therapeutic target for kidney clear cell carcinoma(KIRC).Methods:The cancer genome atlas(TCGA)database was used to analyze the expression of HERC6 in KIRC.The UALCAN database was applied to evaluate the clinical correlation between HERC6 and KIRC.Univariate Cox regression analysis was carried out to construct a prognostic model of HERC6 in KIRC.The correlations between HERC6 expression and immune cell infiltration,immune-related functions,and immune checkpoints were investigated.The potential of HERC6 as a new target for targeted therapy was explored through drug sensitivity experiments.Finally,5-ethynyl-2'-deoxyuridine incorporation assay(EdU),wound-healing,and Transwell assays were conducted to verify the role of HERC6 in the occurrence and progression of KIRC.Results:The expression of HERC6 in KIRC was significantly lower compared with that in normal renal tissues(P<0.001).Patients with low HERC6 expression had a poorer prognosis and less favorable clinicopathological features.Functional enrichment analysis showed that HERC6 was mainly involved in biological processes such as immune response and lipid metabolism,thus mediating the development of KIRC.Immune-related analysis indicated that HERC6 has the potential to be a candidate target for immunotherapy of KIRC.In vitro experiments by overexpressing HERC6 in KIRC cells showed that the proliferation,migration,and invasion abilities were inhibited.Conclusion:HERC6 can serve as a prognostic biomarker and a therapeutic target for KIRC.

关 键 词：肾透明细胞肾细胞癌 HERC6 预后标志物 治疗靶点 

分 类 号：R737.11[医药卫生—肿瘤]