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目的 探讨Rho GTP酶激活蛋白9(ARHGAP9)在肾透明细胞癌(KIRC)中的表达、临床预后价值及与免疫细胞浸润的相关性。方法 基于癌症基因组图谱计划数据库及临床样本验证，比较ARHGAP9在KIRC肿瘤组织与正常组织中的表达差异。通过分层分析，探讨ARHGAP9表达水平及其DNA启动子甲基化状态与患者临床病理特征的关系。利用检索相互作用的基因/蛋白质的搜索工具平台构建ARHGAP9的蛋白互作网络，并对互作基因进行京都基因与基因组百科全书通路富集分析。进一步应用肿瘤免疫评估资源数据库算法，评估ARHGAP9表达与肿瘤微环境中免疫细胞浸润水平的关联。结合Cox比例风险回归模型，评估ARHGAP9表达及关键免疫细胞浸润对KIRC患者预后的独立预测价值。结果 ARHGAP9在多种肿瘤中差异表达并与患者预后相关(P<0.05)。ARHGAP9的mRNA和蛋白表达水平在KIRC中上调(P<0.05)。KIRC中ARHGAP9的mRNA和蛋白表达以及DNA启动子的甲基化水平与组织学分级、TNM分期和淋巴结分期有关(P<0.05)。功能富集分析结果表明，ARHGAP9参与调节鞘脂信号通路、环磷酸腺苷信号通路、Ras信号通路以及Wnt信号通路。ARHGAP9的表达与CD4~+T细胞、CD8~+T细胞、中性粒细胞、树突状细胞、B细胞和巨噬细胞的浸润水平相关(P<0.05)。单因素和多因素Cox回归分析显示，ARHGAP9高表达是KIRC患者预后的独立危险因素。结论 ARHGAP9在KIRC中高表达并与不良预后相关，可能作为KIRC患者预后的可靠生物标志物和治疗的潜在靶点。
Abstract：Objective To investigate the expression, clinical prognostic value, and correlation with immune cell infiltration of Rho GTPase activating protein 9(ARHGAP9) in kidney clear cell carcinoma(KIRC). Methods Based on the The Cancer Genome Atla database, and validation with clinical samples, we compared the expression differences of ARHGAP9 between KIRC tumor tissues and normal tissues. Through stratified analysis, the relationship between ARHGAP9 expression levels and the methylation status of its DNA promoter with patients' clinicopathological characteristics was investigated. The Search Tool for the Retrieval of Interacting Genes/Proteins was utilized to construct a protein interaction network for ARHGAP9, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed on the interacting genes. Furthermore, the Tumor Immune Estimation Resource database algorithm was applied to evaluate the association between ARHGAP9 expression and immune cell infiltration levels in the tumor microenvironment. Combined with Cox proportionalhazards regression models, the independent prognostic value of ARHGAP9 expression and key immune cell infiltration in KIRC patients was assessed. Results ARHGAP9 was differentially expressed in multiple cancers and correlated with patient prognosis(P<0.05). The mRNA and protein expression levels of ARHGAP9 were upregulated in KIRC(P<0.05). In KIRC, ARHGAP9 mRNA and protein expression, as well as DNA promoter methylation levels, were associated with histological grade, pathological stage, and lymph node stage(P<0.05). Functional enrichment analysis results indicated that ARHGAP9 was involved in regulating the sphingolipid signaling pathway, cAMP signaling pathway, Ras signaling pathway, and Wnt signaling pathway. The expression of ARHGAP9 correlated with the infiltration levels of CD4+ T cells, CD8+ T cells, neutrophils, dendritic cells, B cells, and macrophages(P<0.05). Univariate and multivariate Cox regression analyses revealed that high expression of ARHGAP9 was an independent prognostic risk factor for KIRC patients. Conclusion ARHGAP9 is highly expressed in KIRC and associated with poor prognosis, suggesting that it may serve as a reliable prognostic biomarker and a potential therapeutic target for KIRC patients.
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基本信息:
中图分类号:R737.11
引用信息:
[1]王佳龙,殷桂草,李一帆.Rho GTP酶激活蛋白9在肾透明细胞癌中的表达及临床意义的生物信息学分析[J].临床肿瘤学杂志,2026,31(01):25-31.
基金信息:
国家自然科学基金（82002675）; 扬州市科技计划项目（YZ2024120）
2026-01-28
2026-01-28