Wang Guobing, Huang Jinbang, Chen Haiqing, Jiang Chenglu, Jiang Lai, Feng Wenqi, Tian Gang
Yibin Traditional Chinese Medicine Hospital, Yibin, China.
School of Clinical Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, China.
Discov Oncol. 2025 Mar 13;16(1):311. doi: 10.1007/s12672-025-02090-5.
Kidney renal clear cell carcinoma (KIRC) constitutes the primary subtype of renal cell carcinoma, representing 75% to 80% of cases and carrying a substantial cancer-specific mortality rate of up to 24%. Despite advancements in treatment options, KIRC displays notable resistance to conventional therapies, emphasizing the need for innovative targeted immunotherapeutic strategies. Chromatin regulators (CRs), pivotal proteins controlling gene expression and critical biological processes, play a crucial role in the initiation and progression of KIRC. This study employed a multi-omics approach to evaluate the impact of CR-associated genes on KIRC prognosis.
The study utilized the TCGA-KIRC dataset and employed LASSO Cox regression to construct and validate a prognostic model that focuses on genes influencing KIRC prognosis. The research investigated interactions among gene characteristics, clinical parameters, the tumor microenvironment, targeted immunotherapy, and drug responsiveness. Experimental validation, encompassing various techniques such as cell culture, transient transfection, qPCR, Transwell assays, confirmed the robust predictive capability of the BRD9 gene.
The analysis identified the risk score of CRs as an independent factor determining KIRC prognosis. Furthermore, the study introduced a predictive Nomogram model that integrates clinical attributes and risk assessment. Significantly, BRD9 exhibited substantially elevated expression within KIRC cells, underscoring its role in driving cancer cell proliferation, invasion, and migration. These findings suggest the potential for tailored immunotherapy targeting BRD9 in the treatment of KIRC.
This study presents an innovative prognostic framework for KIRC based on multi-omics approaches, seamlessly incorporating CRs. This model holds promise for improving the accuracy of prognosis prediction for KIRC patients, laying a robust foundation for the development of targeted immunotherapies.
肾透明细胞癌（KIRC）是肾细胞癌的主要亚型，占病例的75%至80%，癌症特异性死亡率高达24%。尽管治疗选择有所进展，但KIRC对传统疗法表现出显著抗性，凸显了创新靶向免疫治疗策略的必要性。染色质调节因子（CRs）是控制基因表达和关键生物学过程的关键蛋白，在KIRC的发生和发展中起关键作用。本研究采用多组学方法评估CR相关基因对KIRC预后的影响。
该研究利用TCGA-KIRC数据集，采用LASSO Cox回归构建并验证了一个侧重于影响KIRC预后基因的预后模型。该研究调查了基因特征、临床参数、肿瘤微环境、靶向免疫治疗和药物反应性之间的相互作用。包括细胞培养、瞬时转染、qPCR、Transwell分析等各种技术的实验验证证实了BRD9基因强大的预测能力。
分析确定CRs的风险评分是决定KIRC预后的独立因素。此外，该研究引入了一个整合临床特征和风险评估的预测列线图模型。值得注意的是，BRD9在KIRC细胞中的表达显著升高，突显了其在驱动癌细胞增殖、侵袭和迁移中的作用。这些发现表明针对BRD9的定制免疫疗法在KIRC治疗中的潜力。
本研究基于多组学方法提出了一种创新的KIRC预后框架，无缝纳入了CRs。该模型有望提高KIRC患者预后预测的准确性，为靶向免疫疗法的开发奠定坚实基础。
