Dong Jianda, Fan Lailai, Wu Qiaolin, Zheng Zhouci
Department of Neck Surgery, The Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Urinary Surgery, The Second Affiliated Hospital and Yuying, Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
BMC Urol. 2025 Mar 28;25(1):62. doi: 10.1186/s12894-025-01744-4.
Kidney clear cell carcinoma (KIRC) stands as one of the most prevalent primary malignant tumors, showcasing significant heterogeneity within the urological system. However, the precise molecular mechanisms underpinning tumorigenesis in KIRC remain elusive. While Retinoid X receptor γ (RXRG) has been implicated in various diseases and human cancers, its specific role in KIRC remains undetermined. This research aimed to investigate the involvement of RXRG in KIRC pathogenesis.
Quantitative real-time polymerase chain reaction was performed to evaluate the expression levels of RXRG in KIRC. Utilizing RNA-seq data and corresponding clinicopathological information from The Cancer Genome Atlas (TCGA) database, we embarked on an analysis to ascertain the prognostic significance of RXRG in KIRC. Furthermore, bioinformatics analyses were employed to delineate the preliminary molecular mechanisms through which RXRG operates in KIRC tumorigenesis.
Our findings revealed a significant downregulation of RXRG in KIRC tumor tissues compared to normal kidney tissues, as evidenced in local and TCGA cohorts. Diminished RXRG expression correlated with adverse clinicopathological characteristics, including larger tumor size, higher clinical stage, and advanced histologic grade. Cox regression analyses unveiled that reduced RXRG expression was associated with poorer overall survival (OS) and disease-free survival (DFS) rates in KIRC patients. Bioinformatics analyses indicated that the RXRG-related differentially expressed genes (DEGs) were involved in tumorigenesis and metabolism by regulating a series of signaling pathways. Using ssGSEA, we found that RXRG expression was significantly associated with NK cells and macrophages.
Our study provides new insights and evidence that RXRG is involved in the tumorigenesis of KIRC and may be a suitable target for immunotherapy in KIRC.
肾透明细胞癌（KIRC）是最常见的原发性恶性肿瘤之一，在泌尿系统中表现出显著的异质性。然而，KIRC肿瘤发生的确切分子机制仍不清楚。虽然视黄酸X受体γ（RXRG）已被证明与多种疾病和人类癌症有关，但其在KIRC中的具体作用仍未确定。本研究旨在探讨RXRG在KIRC发病机制中的作用。
采用定量实时聚合酶链反应（qRT-PCR）检测KIRC中RXRG的表达水平。利用来自癌症基因组图谱（TCGA）数据库的RNA测序数据和相应的临床病理信息，我们进行了分析，以确定RXRG在KIRC中的预后意义。此外，我们还利用生物信息学分析来描述RXRG在KIRC肿瘤发生中发挥作用的初步分子机制。
我们的研究结果显示，与正常肾组织相比，KIRC肿瘤组织中RXRG表达显著下调，这在本地队列和TCGA队列中均得到证实。RXRG表达降低与不良临床病理特征相关，包括肿瘤体积较大、临床分期较高和组织学分级较高。Cox回归分析表明，RXRG表达降低与KIRC患者较差的总生存期（OS）和无病生存期（DFS）相关。生物信息学分析表明，RXRG相关的差异表达基因（DEGs）通过调节一系列信号通路参与肿瘤发生和代谢。使用单样本基因集富集分析（ssGSEA），我们发现RXRG表达与自然杀伤细胞（NK细胞）和巨噬细胞显著相关。
我们的研究提供了新的见解和证据，表明RXRG参与了KIRC的肿瘤发生，可能是KIRC免疫治疗的合适靶点。
