CKAP4 and PLOD2 as novel prognostic biomarkers in hepatocellular carcinoma: a proteomics-driven risk stratification model.

IF 4.6 2区生物学 Q2 CELL BIOLOGY

Frontiers in Cell and Developmental Biology Pub Date : 2025-07-02 eCollection Date: 2025-01-01 DOI:10.3389/fcell.2025.1577161

Qiulong Lu, Zhao Cao, Yueting Xiong, Junqiang Huang, Huan Zeng, Zhijian Chen, You Shu, Yahan Tan, Xiaoling Long, Xiaohui Liu, Hong Shu

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Abstract

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.

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CKAP4和PLOD2作为新的肝细胞癌预后生物标志物：蛋白质组学驱动的风险分层模型

背景：肝细胞癌（HCC）患者的预后是一个研究热点。本研究旨在利用数据独立获取质谱法（DIA-MS）识别新的HCC预后蛋白标志物，并建立一个综合预测模型，以增强临床决策和患者分层。方法：采用DIA-MS对31例不同预后的HCC患者进行有价值的预后生物标志物鉴定。采用免疫组织化学（IHC）建立并验证了预后模型。结果：细胞骨架相关膜蛋白4 （CKAP4）和前胶原-赖氨酸，2-氧葡萄糖酸酯5-双加氧酶2 （PLOD2）被确定为关键预后蛋白，表达水平高与预后不良相关。免疫组化验证证实了CKAP4和PLOD2的预后价值。与单个指标相比，包含AJCC分期和CKAP4和PLOD2组合的nomogram预测总生存期（OS）的稳定性更强。该模型预测结果的一致性指数（C-index）为0.738 (95% CI, 0.698-0.779)，并将患者显著分层为不同的危险组（P < 0.001）。结论：本研究确定CKAP4和PLOD2是HCC的新型预后蛋白标志物。将这些分子标记物与AJCC分期相结合，开发的nomogram （nomogram）有望预测HCC患者的OS和风险分层。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Cell and Developmental Biology Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

9.70

自引率

3.60%

发文量

2531

审稿时长

12 weeks

期刊介绍： Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board. The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology. With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.