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整合生物信息学与 EVI2A 表达研究:揭示其在肾透明细胞癌中的免疫和预后意义。

Integrative bioinformatics and exploration of EVI2A expression: unraveling its immunological and prognostic implications in kidney renal clear cell carcinoma.

机构信息

Department of Urology, Fujian Medical University Union Hospital, Fuzhou, 350000, China.

Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, 350000, China.

出版信息

Oncol Res. 2024 Oct 16;32(11):1733-1746. doi: 10.32604/or.2024.050851. eCollection 2024.

Abstract

EVI2A has emerged as a significant biomarker in various diseases; however, its biological role and mechanism in kidney renal clear cell carcinoma (KIRC) remains unexplored. We used TCGA and GEO databases to analyze EVI2A gene expression comprehensively and performed pan-cancer assessments. Clinical relevance was evaluated through Kaplan-Meier analysis and ROC curves. The gene's immune relevance was explored through analyses of the tumor microenvironment (TME), Tumor Immune Single-cell Hub (TISCH), immune checkpoints, and immunotherapy sensitivity. Our results indicate that EVI2A expression is upregulated in KIRC, showing correlations with tumor grade and T/N/M stage. EVI2A demonstrates high diagnostic accuracy (AUC=0.906) and predicts poor overall and progression-free survival in KIRC patients. Furthermore, EVI2A expression exhibits significant associations with immunity, including TME scores and specific immune cell types such as Tfh cells, CD4 memory T cells, and CD8+ T cells. Elevated EVI2A expression suggests increased sensitivity to PD-1/CTLA-4 and tyrosine kinase inhibitors. assays confirmed the impact of EVI2A on KIRC behavior, with its knockdown resulting in reduced cell proliferation and migration. In conclusion, our comprehensive analysis identifies EVI2A as a promising biomarker and a novel therapeutic target for intervening in KIRC. These findings hold significant implications for further research and potential clinical applications.

摘要

EVI2A 已成为多种疾病中的重要生物标志物;然而,其在肾透明细胞癌(KIRC)中的生物学作用和机制仍未被探索。我们使用 TCGA 和 GEO 数据库全面分析了 EVI2A 基因表达,并进行了泛癌评估。通过 Kaplan-Meier 分析和 ROC 曲线评估了临床相关性。通过肿瘤微环境(TME)、肿瘤免疫单细胞图谱(TISCH)、免疫检查点和免疫治疗敏感性分析,探讨了该基因的免疫相关性。结果表明,EVI2A 在 KIRC 中表达上调,与肿瘤分级和 T/N/M 分期相关。EVI2A 在 KIRC 患者中具有较高的诊断准确性(AUC=0.906),并预测总体生存率和无进展生存率较差。此外,EVI2A 表达与免疫有显著相关性,包括 TME 评分和特定免疫细胞类型,如滤泡辅助性 T 细胞(Tfh)、CD4 记忆 T 细胞和 CD8+T 细胞。EVI2A 表达升高提示对 PD-1/CTLA-4 和酪氨酸激酶抑制剂的敏感性增加。体外和体内实验证实了 EVI2A 对 KIRC 行为的影响,其敲低导致细胞增殖和迁移减少。综上所述,我们的综合分析将 EVI2A 确定为一种有前途的生物标志物和干预 KIRC 的新治疗靶点。这些发现对进一步的研究和潜在的临床应用具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3418/11497181/b962afe6d525/OncolRes-32-50851-f001.jpg

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