Wang Zheyu, Li Hongze, Hou Xiaolong, Zhang Senyu, Deng Kai, Wang Nianqiang, Wang Wei, Zhu Yuyan
Department of Urology, The First Hospital of China Medical University, Shenyang, 110001, China.
Department of Gynaecology, The First Hospital of China Medical University, Shenyang, 110001, China.
BMC Cancer. 2025 Aug 13;25(1):1314. doi: 10.1186/s12885-025-14749-x.
Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system, accounting for approximately 80% of urinary tract malignancies, with clear cell renal cell carcinoma (ccRCC) being the most prevalent subtype. Despite its high incidence, the pathogenesis of ccRCC remains incompletely elucidated, and limitations persist in early diagnosis, targeted therapy, and immunotherapy. Based on emerging evidence highlighting the critical role of liquid-liquid phase separation (LLPS) in tumor proliferation and invasion, this study leveraged multiple ccRCC cohorts to employ Mendelian randomization (MR) and ultimately developed a novel Bidirectional Liquid-Liquid Phase Separation-associated Index (B-LLPSI) using LASSO regression, aiming to predict patient prognosis and therapeutic response. Notably, B-LLPSI demonstrates substantial potential as a universal prognostic indicator across multiple cancer types, underpinning its prospective application in individualized oncology. Paradoxically, while high B-LLPSI levels correlate with poorer patient prognosis, they simultaneously predict enhanced responsiveness to immunotherapy. Furthermore, the B-LLPSI signature was found to be upregulated in tumor tissues and capable of promoting tumor proliferation and invasion. In summary, B-LLPSI holds promise as a robust and independent prognostic tool for diverse cancers, providing critical insights for formulating individualized treatment strategies.
肾细胞癌（RCC）是泌尿系统常见的恶性肿瘤，约占尿路恶性肿瘤的80%，其中透明细胞肾细胞癌（ccRCC）是最常见的亚型。尽管其发病率高，但ccRCC的发病机制仍未完全阐明，在早期诊断、靶向治疗和免疫治疗方面仍存在局限性。基于新出现的证据突出了液-液相分离（LLPS）在肿瘤增殖和侵袭中的关键作用，本研究利用多个ccRCC队列采用孟德尔随机化（MR），最终使用LASSO回归开发了一种新型的双向液-液相分离相关指数（B-LLPSI），旨在预测患者的预后和治疗反应。值得注意的是，B-LLPSI作为多种癌症类型的通用预后指标具有巨大潜力，为其在个体化肿瘤学中的前瞻性应用奠定了基础。矛盾的是，虽然高B-LLPSI水平与患者预后较差相关，但它们同时预测对免疫治疗的反应增强。此外，发现B-LLPSI特征在肿瘤组织中上调，并且能够促进肿瘤增殖和侵袭。总之，B-LLPSI有望成为多种癌症强大而独立的预后工具，为制定个体化治疗策略提供关键见解。
