肝细胞癌组织中的蛋白质异构体模式：肿瘤标志物相关方面

Proteoform Patterns in Hepatocellular Carcinoma Tissues: Aspects of Oncomarkers.

作者信息

Zorina Elena, Ronzhina Natalia, Legina Olga, Klopov Nikolai, Zgoda Victor, Naryzhny Stanislav

机构信息

Institute of Biomedical Chemistry, Pogodinskaya, 10, Moscow 119121, Russia.

Petersburg Nuclear Physics Institute Named by B. P. Konstantinov of National Research Centre "Kurchatov Institute", Gatchina 188300, Russia.

出版信息

Proteomes. 2025 Jul 1;13(3):27. doi: 10.3390/proteomes13030027.

DOI:10.3390/proteomes13030027

PMID:40700271

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12285994/

Abstract

BACKGROUND

Human proteins exist in numerous modifications-proteoforms-which are promising targets for biomarker studies. In this study, we aimed to generate comparative proteomics data, including proteoform patterns, from hepatocellular carcinoma (HCC) and nonmalignant liver tissues.

METHODS

To investigate protein profiles and proteoform patterns, we employed a panoramic, integrative top-down proteomics approach: two-dimensional gel electrophoresis (2DE) coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS).

RESULTS

We visualized over 2500 proteoform patterns per sample type, enabling the identification of distinct protein signatures and common patterns differentiating nonmalignant and malignant liver cells. Among these, 1270 protein patterns were uniformly observed across all samples. Additionally, 38 proteins-including pyruvate kinase PKM (KPYM), annexin A2 (ANXA2), and others-exhibited pronounced differences in proteoform patterns between nonmalignant and malignant tissues.

CONCLUSIONS

Most proteoform patterns of the same protein were highly similar, with the dominant peak corresponding to theoretical (unmodified) protein parameters. However, certain proteins displayed altered proteoform patterns and additional proteoforms in cancer compared to controls. These proteins were prioritized for further characterization.

摘要

背景

人类蛋白质存在多种修饰形式——蛋白质异构体，它们是生物标志物研究的潜在靶点。在本研究中，我们旨在生成来自肝细胞癌（HCC）和非恶性肝组织的比较蛋白质组学数据，包括蛋白质异构体模式。

方法

为了研究蛋白质谱和蛋白质异构体模式，我们采用了一种全景式、综合的自上而下蛋白质组学方法：二维凝胶电泳（2DE）结合液相色谱 - 电喷雾电离 - 串联质谱（LC - ESI - MS/MS）。

结果

我们在每种样本类型中可视化了超过2500种蛋白质异构体模式，从而能够识别区分非恶性和恶性肝细胞的独特蛋白质特征和常见模式。其中，在所有样本中均一致观察到1270种蛋白质模式。此外，38种蛋白质——包括丙酮酸激酶PKM（KPYM）、膜联蛋白A2（ANXA2）等——在非恶性和恶性组织的蛋白质异构体模式上表现出明显差异。