Epigenetic Alterations in Renal Clear Cell Carcinoma: A Comprehensive Expression and Clinical Outcome Analysis

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Dafei Weng, Zhenqian Qin, Xuefeng Yuan, Xuping Jiang, Hua Rui
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Abstract

Renal clear cell carcinoma (ccRCC) presents a unique landscape of genetic and epigenetic modifications, the understanding of which is crucial for the development of targeted therapies and improved prognostication. This study explores the differential expression of histone-related genes (HRGs) in ccRCC and correlates these findings with patient clinical outcomes. By leveraging the Cancer Genome Atlas (TCGA) data, we performed a robust multidimensional analysis of HRG expression profiles in ccRCC versus adjacent normal tissues. Our results demonstrate a significant upregulation of several key epigenetic regulators, including UHRF1, KDM5A, EZH2, PRDM6, and TWIST1, in tumor samples, with statistical significance suggesting their involvement in tumorigenesis and progression. Paired expression analysis within patient-matched samples confirmed the consistency of overexpression in tumors. The prognostic relevance of these genes was underscored through survival analyses, which revealed a clear stratification of patients into distinct risk categories based on their expression profiles. The integration of these genetic markers with clinical parameters facilitated the development of a predictive nomogram, yielding a quantifiable tool for survival prediction. Our comprehensive analysis elucidates the profound impact of epigenetic dysregulation in ccRCC and proposes a novel set of biomarkers for disease diagnosis, prognostic stratification, and potential therapeutic targeting, marking a significant stride toward precision oncology in renal cancer.

Abstract Image

肾透明细胞癌的表观遗传改变:综合表达和临床结果分析
肾透明细胞癌(ccRCC)呈现出独特的遗传和表观遗传修饰景观,对其的理解对于开发靶向治疗和改善预后至关重要。本研究探讨了组蛋白相关基因(HRGs)在ccRCC中的差异表达,并将这些发现与患者临床结果联系起来。通过利用癌症基因组图谱(TCGA)数据,我们对ccRCC与邻近正常组织中HRG表达谱进行了强大的多维分析。我们的研究结果表明,几个关键的表观遗传调控因子,包括UHRF1、KDM5A、EZH2、PRDM6和TWIST1,在肿瘤样本中显著上调,具有统计学意义,表明它们参与了肿瘤的发生和进展。配对表达分析在患者匹配样本中证实了肿瘤中过表达的一致性。通过生存分析,这些基因的预后相关性得到了强调,这揭示了基于其表达谱的患者明确分层为不同的风险类别。这些遗传标记与临床参数的整合促进了预测nomogram的发展,为生存预测提供了一种可量化的工具。我们的综合分析阐明了表观遗传失调在ccRCC中的深远影响,并提出了一套新的疾病诊断、预后分层和潜在治疗靶向的生物标志物,标志着肾癌精准肿瘤学的重要一步。
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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
226
审稿时长
6 months
期刊介绍: The Journal of Clinical Pharmacy and Therapeutics provides a forum for clinicians, pharmacists and pharmacologists to explore and report on issues of common interest. Reports and commentaries on current issues in medical and pharmaceutical practice are encouraged. Papers on evidence-based clinical practice and multidisciplinary collaborative work are particularly welcome. Regular sections in the journal include: editorials, commentaries, reviews (including systematic overviews and meta-analyses), original research and reports, and book reviews. Its scope embraces all aspects of clinical drug development and therapeutics, including: Rational therapeutics Evidence-based practice Safety, cost-effectiveness and clinical efficacy of drugs Drug interactions Clinical impact of drug formulations Pharmacogenetics Personalised, stratified and translational medicine Clinical pharmacokinetics.
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