High intratumoral heterogeneity in clear cell renal cell carcinoma is associated with reduced immune response and survival.

IF 1.7 3区医学 Q4 ANDROLOGY

Translational andrology and urology Pub Date : 2025-05-30 Epub Date: 2025-05-27 DOI:10.21037/tau-2024-741

Qizhou Yang, Yuying Han, Xu Liu, Liting Xue, Zhengguo Ji, Haihong Ye

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引用次数: 0

Abstract

Background: Clear cell renal cell carcinoma (ccRCC) exhibits high intratumor heterogeneity (ITH), which drives progression, metastasis, and treatment resistance. Nevertheless, clinically applicable tools for predicting patient prognosis based on ITH remain unavailable, and the association between ITH and immune cell response is a matter of debate. The objective of this study was to establish ITH as a clinically relevant biomarker capable of predicting outcomes and informing treatment strategies in ccRCC.

Methods: The Bioconductor R package Maftools was used to analyze somatic variants of ccRCC from The Cancer Genome Atlas (TCGA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) was used to estimate immune cell compositions. A mutant-allele tumor heterogeneity (MATH) algorithm was used to measure ITH, and we explored its correlation with clinical parameters and immune cell response.

Results: Our analysis revealed that lower MATH values were significantly associated with increased infiltration of activated dendritic cells (P=0.048) and reduced levels of immunosuppressive regulatory T cells (Tregs; P=0.02), suggesting enhanced antitumor immunity in less heterogeneous tumors. Conversely, high MATH values correlated with worse overall survival and a suppressed immune microenvironment. These findings support the potential of MATH as a stratification biomarker for ccRCC patients, helping identify those who may benefit from immunotherapy or targeted therapies.

Conclusions: High MATH value correlates with worse survival and decreased immune response in ccRCC patients.

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透明细胞肾细胞癌的高肿瘤内异质性与免疫应答和生存率降低有关。

背景：透明细胞肾细胞癌（ccRCC）表现出高度的肿瘤内异质性（ITH），这导致了进展、转移和治疗抵抗。然而，基于ITH的临床应用预测患者预后的工具仍然不可用，并且ITH与免疫细胞反应之间的关系是一个有争议的问题。本研究的目的是建立ITH作为临床相关的生物标志物，能够预测ccRCC的预后并为治疗策略提供信息。方法：采用Bioconductor R软件包Maftools分析来自Cancer Genome Atlas （TCGA）的ccRCC体细胞变异，并采用CIBERSORT（估计RNA转录物相对亚集的细胞类型鉴定）估计免疫细胞组成。采用突变-等位基因肿瘤异质性（MATH）算法测量ITH，并探讨其与临床参数和免疫细胞反应的相关性。结果：我们的分析显示，较低的MATH值与活化树突状细胞浸润增加（P=0.048）和免疫抑制调节性T细胞(Tregs；P=0.02)，提示异质性较低的肿瘤抗肿瘤免疫增强。相反，较高的MATH值与较差的总生存率和抑制的免疫微环境相关。这些发现支持了MATH作为ccRCC患者分层生物标志物的潜力，有助于识别那些可能从免疫治疗或靶向治疗中受益的患者。结论：高MATH值与ccRCC患者生存差和免疫应答降低相关。

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来源期刊

Translational andrology and urology Medicine-Urology

CiteScore

4.10

自引率

5.00%

发文量

期刊介绍： ranslational Andrology and Urology (Print ISSN 2223-4683; Online ISSN 2223-4691; Transl Androl Urol; TAU) is an open access, peer-reviewed, bi-monthly journal (quarterly published from Mar.2012 - Dec. 2014). The main focus of the journal is to describe new findings in the field of translational research of Andrology and Urology, provides current and practical information on basic research and clinical investigations of Andrology and Urology. Specific areas of interest include, but not limited to, molecular study, pathology, biology and technical advances related to andrology and urology. Topics cover range from evaluation, prevention, diagnosis, therapy, prognosis, rehabilitation and future challenges to urology and andrology. Contributions pertinent to urology and andrology are also included from related fields such as public health, basic sciences, education, sociology, and nursing.