Lu Qiulong, Cao Zhao, Xiong Yueting, Huang Junqiang, Zeng Huan, Chen Zhijian, Shu You, Tan Yahan, Long Xiaoling, Liu Xiaohui, Shu Hong
Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China.
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Front Cell Dev Biol. 2025 Jul 2;13:1577161. doi: 10.3389/fcell.2025.1577161. eCollection 2025.
The prognosis of patients with hepatocellular carcinoma (HCC) is a research hotspot. This study aimed to identify novel prognostic protein markers for HCC using data-independent acquisition mass spectrometry (DIA-MS) and develop an integrative predictive model to enhance clinical decision-making and patient stratification.
DIA-MS were implemented to identify valuable prognostic HCC biomarkers in 31 patients with different prognoses. A prognostic model was developed and validated using immunohistochemistry (IHC).
Cytoskeleton-associated membrane protein 4 (CKAP4) and procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2) were identified as key prognostic proteins, with higher expression levels associated with poor prognosis. Immunohistochemical validation confirmed the prognostic value of CKAP4 and PLOD2. A nomogram incorporating AJCC stage and the combination of CKAP4 and PLOD2 demonstrated superior predictive Sability for overall survival (OS) compared to individual indicators. The model predicted an outcome with a concordance index (C-index) of 0.738 (95% CI, 0.698-0.779) and significantly stratified patients into distinct risk groups ( < 0.001).
In conclusion, this study identified CKAP4 and PLOD2 as novel prognostic protein markers for HCC. The developed nomogram, integrating these molecular markers with AJCC stage, shows promise in predicting OS and stratifying risk in HCC patients.
肝细胞癌（HCC）患者的预后是一个研究热点。本研究旨在使用数据非依赖采集质谱法（DIA-MS）识别HCC新的预后蛋白标志物，并开发一种综合预测模型以改善临床决策和患者分层。
采用DIA-MS在31例不同预后的患者中识别有价值的HCC预后生物标志物。使用免疫组织化学（IHC）开发并验证了一种预后模型。
细胞骨架相关膜蛋白4（CKAP4）和脯氨酰羟化酶2（PLOD2）被确定为关键预后蛋白，其较高的表达水平与不良预后相关。免疫组织化学验证证实了CKAP4和PLOD2的预后价值。与单个指标相比，结合美国癌症联合委员会（AJCC）分期以及CKAP4和PLOD2组合的列线图对总生存期（OS）显示出更好的预测能力。该模型预测结果的一致性指数（C指数）为0.738（95%CI，0.698 - 0.779），并将患者显著分层为不同风险组（P < 0.001）。
总之，本研究确定CKAP4和PLOD2为HCC新的预后蛋白标志物。所开发的列线图将这些分子标志物与AJCC分期相结合，在预测HCC患者的OS和分层风险方面显示出前景。
