ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1577161
This article is part of the Research TopicHepatobiliary tumors: Molecular Targets and TherapeuticsView all 5 articles
CKAP4 and PLOD2 as Novel Prognostic Biomarkers in Hepatocellular Carcinoma: A Proteomics-Driven Risk Stratification Model
Provisionally accepted
Qiulong Lu1Zhao Cao2Yueting Xiong3Junqiang Huang2Huan Zeng1Zhijian Chen2You Shu1Yahan Tan1Xiaoling Long1Xiaohui Liu4*
Hong Shu1*- 1Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
- 2Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangx, China
- 3State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory,Xiamen University, Xiamen, China
- 4Institute of Translational Medicine, Shanghai Jiao Tong University, Shangahi, China
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Background: 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.Methods: 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).Results: 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 (P < 0.001). Conclusion: 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.
Keywords: HCC, DIA-MS proteomics, Prognosis biomarkers, Prognostic model, PLOD2, CKAP4
Received: 15 Feb 2025; Accepted: 06 Jun 2025.
Copyright: © 2025 Lu, Cao, Xiong, Huang, Zeng, Chen, Shu, Tan, Long, Liu and Shu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiaohui Liu, Institute of Translational Medicine, Shanghai Jiao Tong University, Shangahi, 200240, China
Hong Shu, Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, China
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