Li Jianhao, Chen Han, Bai Lang, Tang Hong
Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China.
Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, 610041, China.
Biol Direct. 2025 Jan 6;20(1):2. doi: 10.1186/s13062-025-00592-4.
Liquid-liquid phase separation (LLPS) is essential for the formation of membraneless organelles and significantly influences cellular compartmentalization, chromatin remodeling, and gene regulation. Previous research has highlighted the critical function of liquid-liquid biopolymers in the development of hepatocellular carcinoma (HCC).
This study conducted a comprehensive review of 3,685 liquid-liquid biopolymer regulators, leading to the development of a LLPS related Prognostic Risk Score (LPRS) for HCC through bootstrap-based univariate Cox, Random Survival Forest (RSF), and LASSO analyses. A prognostic nomogram for HCC patients was developed using LPRS and other clinicopathological factors. We utilized SurvSHAP to identify key genes within the LPRS influencing HCC prognosis. To validate our findings, we collected 49 HCC cases along with adjacent tissue samples and confirmed the correlation between DCAF13 expression and HCC progression through qRT-PCR analysis and in vitro experiments.
LPRS was established with 8 LLPS-related genes (TXN, CBX2, DCAF13, SLC2A1, KPNA2, FTCD, MAPT, and SAC3D1). Further research indicated that a high LPRS is closely associated with vascular invasion, histological grade (G3-G4), and TNM stage (III-IV) in HCC, concurrently establishing LPRS as an independent risk factor for prognosis. A nomogram that integrates LPRS with TNM staging and patient age markedly improves the predictive accuracy of survival outcomes for HCC patients. Our findings suggest that increased DCAF13 expression in HCC plays a crucial role in cancer progression and angiogenesis. Navitoclax has emerged as a promising treatment for HCC patients with high LPRS levels, offering a novel therapeutic direction by targeting LLPS.
We have formulated a novel LPRS model that is capable of accurately predicting the clinical prognosis and drug sensitivity of HCC. DCAF13 might play a pivotal role in malignant progression mediated by LLPS.
液-液相分离（LLPS）对于无膜细胞器的形成至关重要，并显著影响细胞区室化、染色质重塑和基因调控。先前的研究强调了液-液生物聚合物在肝细胞癌（HCC）发展中的关键作用。
本研究对3685种液-液生物聚合物调节因子进行了全面综述，通过基于自抽样的单变量Cox分析、随机生存森林（RSF）分析和LASSO分析，开发了一种用于HCC的LLPS相关预后风险评分（LPRS）。利用LPRS和其他临床病理因素为HCC患者制定了预后列线图。我们使用SurvSHAP来识别LPRS中影响HCC预后的关键基因。为了验证我们的发现，我们收集了49例HCC病例以及相邻组织样本，并通过qRT-PCR分析和体外实验证实了DCAF13表达与HCC进展之间的相关性。
LPRS由8个与LLPS相关的基因（TXN、CBX2、DCAF13、SLC2A1、KPNA2、FTCD、MAPT和SAC3D1）建立。进一步研究表明，高LPRS与HCC中的血管侵犯、组织学分级（G3-G4）和TNM分期（III-IV）密切相关，同时将LPRS确立为预后的独立危险因素。将LPRS与TNM分期和患者年龄相结合的列线图显著提高了HCC患者生存结局的预测准确性。我们的研究结果表明，HCC中DCAF13表达的增加在癌症进展和血管生成中起关键作用。Navitoclax已成为治疗高LPRS水平HCC患者的一种有前景的治疗方法，通过靶向LLPS提供了一种新的治疗方向。
我们制定了一种新型LPRS模型，能够准确预测HCC的临床预后和药物敏感性。DCAF13可能在由LLPS介导的恶性进展中起关键作用。
