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

IF 2 4区 医学 Q3 ONCOLOGY Oncology Research Pub Date : 2024-10-16 eCollection Date: 2024-01-01 DOI:10.32604/or.2024.050851
Rong Liu, Sheng Li, Situ Xiong, Fucun Zheng, Xiangpeng Zhan, Jin Zeng, Bin Fu, Songhui Xu, Shaoxing Zhu, R U Chen
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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. In vitro 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.

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EVI2A 表达的综合生物信息学和体外探索:揭示其在肾透明细胞癌中的免疫学和预后意义。
EVI2A已成为多种疾病的重要生物标志物,但其在肾透明细胞癌(KIRC)中的生物学作用和机制仍未得到探索。我们利用 TCGA 和 GEO 数据库全面分析了 EVI2A 基因的表达,并进行了泛癌症评估。通过 Kaplan-Meier 分析和 ROC 曲线评估了临床相关性。通过分析肿瘤微环境(TME)、肿瘤免疫单细胞中心(TISCH)、免疫检查点和免疫疗法敏感性,探讨了该基因的免疫相关性。我们的研究结果表明,EVI2A 在 KIRC 中表达上调,与肿瘤分级和 T/N/M 分期相关。EVI2A 具有很高的诊断准确性(AUC=0.906),可预测 KIRC 患者较差的总生存期和无进展生存期。此外,EVI2A 的表达与免疫有显著的关联,包括 TME 评分和特定的免疫细胞类型,如 Tfh 细胞、CD4 记忆 T 细胞和 CD8+ T 细胞。EVI2A 表达升高表明对 PD-1/CTLA-4 和酪氨酸激酶抑制剂的敏感性增加。体外实验证实了 EVI2A 对 KIRC 行为的影响,其敲除会导致细胞增殖和迁移减少。总之,我们的综合分析确定了 EVI2A 是一种有前景的生物标记物,也是干预 KIRC 的新型治疗靶点。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。
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来源期刊
Oncology Research
Oncology Research 医学-肿瘤学
CiteScore
4.40
自引率
0.00%
发文量
56
审稿时长
3 months
期刊介绍: Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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