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通过全面定量组织蛋白质组学分析鉴定潜在的枢纽蛋白作为肝细胞癌的治疗诊断靶点

Identification of Potential Hub Proteins as Theragnostic Targets in Hepatocellular Carcinoma through Comprehensive Quantitative Tissue Proteomics Analysis.

作者信息

Abedin Quratul, Bibi Kulsoom, von Kriegsheim Alex, Hashim Zehra, Ilyas Amber

机构信息

Dr. Zafar H. Zaidi Center for Proteomics, University of Karachi, Karachi, Sindh, Pakistan.

University of Edinburgh, Edinburgh, Scotland, UK.

出版信息

Cancer Inform. 2025 May 14;24:11769351251336923. doi: 10.1177/11769351251336923. eCollection 2025.

DOI:10.1177/11769351251336923
PMID:40375878
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12078984/
Abstract

OBJECTIVE

Hepatocellular carcinoma (HCC) is the most common primary liver cancer mainly caused by hepatitis viral infection. Early stage diagnosis is still challenging due to its asymptomatic behavior so there is an urgent need for effective biomarkers. This study aimed to identify effective diagnostic biomarker or therapeutic target for HCC.

METHOD

Label-free quantitative mass spectrometry was performed to analyze protein expression in HCC and control tissues. Protein-protein interaction (PPI) analysis was done using the STRING database and hub proteins were identified by Cytohubba. The survival analysis and expressions profiling of hub proteins were performed by using GEPIA. Functional and pathway enrichment analysis were carried out using Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG).

RESULTS

A total of 1539 proteins were identified, of which 116 were differentially expressed proteins (DEPs). PPI network analysis revealed 10 hub proteins; EGFR, GAPDH, HSP90AA1, MMP9, PTPRC, CD44, ANXA5, PECAM1, MMP2, and CDK1. Among these, GAPDH, MMP9, ANXA5, HSP90AA1, and CDK1 were significantly associated with low survival rate ( ⩽ .05). Moreover, MMP9 and CDK1 were showed significantly increased expression in tumor tissues as compared to control ( ⩽ .05). The GO analysis based on biological process, cellular components and molecular function indicated that DEPs were enriched in stress response, vesicle and extracellular space, protein binding and enzyme activity. The KEGG pathway analysis showed that the thyroid hormone synthesis pathway is the most enriched.

CONCLUSION

The hub proteins GAPDH, HSP90AA1, MMP9, ANXA5, and CDK1 demonstrated significant prognostic potential, could be used as promising theragnostic biomarkers for HCC.

摘要

目的

肝细胞癌（HCC）是最常见的原发性肝癌，主要由肝炎病毒感染引起。由于其无症状表现，早期诊断仍具有挑战性，因此迫切需要有效的生物标志物。本研究旨在鉴定HCC的有效诊断生物标志物或治疗靶点。

方法

采用无标记定量质谱法分析HCC组织和对照组织中的蛋白质表达。使用STRING数据库进行蛋白质-蛋白质相互作用（PPI）分析，并通过Cytohubba鉴定枢纽蛋白。使用GEPIA进行枢纽蛋白的生存分析和表达谱分析。使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）进行功能和通路富集分析。

结果

共鉴定出1539种蛋白质，其中116种为差异表达蛋白（DEP）。PPI网络分析揭示了10种枢纽蛋白；表皮生长因子受体（EGFR）、甘油醛-3-磷酸脱氢酶（GAPDH）、热休克蛋白90α家族成员1（HSP90AA1）、基质金属蛋白酶9（MMP9）、蛋白酪氨酸磷酸酶受体C（PTPRC）、CD44分子（CD44）、膜联蛋白A5（ANXA5）、血小板内皮细胞黏附分子1（PECAM1）、基质金属蛋白酶2（MMP2）和细胞周期蛋白依赖性激酶1（CDK1）。其中，GAPDH、MMP9、ANXA5、HSP90AA1和CDK1与低生存率显著相关（P≤0.05）。此外，与对照相比，MMP9和CDK1在肿瘤组织中的表达显著增加（P≤0.05）。基于生物过程、细胞成分和分子功能的GO分析表明，DEP在应激反应、囊泡和细胞外空间、蛋白质结合和酶活性中富集。KEGG通路分析表明，甲状腺激素合成通路是最富集的。

结论

枢纽蛋白GAPDH、HSP90AA1、MMP9、ANXA5和CDK1具有显著的预后潜力，可作为HCC有前景的诊疗生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360a/12078984/99ae709e5ed7/10.1177_11769351251336923-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360a/12078984/8cba358dc9a7/10.1177_11769351251336923-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360a/12078984/1aed765791de/10.1177_11769351251336923-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360a/12078984/d321b310efef/10.1177_11769351251336923-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360a/12078984/a5f85602bb1d/10.1177_11769351251336923-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360a/12078984/c221ddd15ce3/10.1177_11769351251336923-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360a/12078984/99ae709e5ed7/10.1177_11769351251336923-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360a/12078984/8cba358dc9a7/10.1177_11769351251336923-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360a/12078984/1aed765791de/10.1177_11769351251336923-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360a/12078984/d321b310efef/10.1177_11769351251336923-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360a/12078984/a5f85602bb1d/10.1177_11769351251336923-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360a/12078984/c221ddd15ce3/10.1177_11769351251336923-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/360a/12078984/99ae709e5ed7/10.1177_11769351251336923-fig6.jpg

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Pharmaceutics. 2023 Aug 14;15(8):2130. doi: 10.3390/pharmaceutics15082130.
2
Annexins A2 and A5 are potential early biomarkers of hepatocarcinogenesis.膜联蛋白 A2 和 A5 是肝癌发生的潜在早期生物标志物。
Sci Rep. 2023 Apr 28;13(1):6948. doi: 10.1038/s41598-023-34117-8.
3
Predictors of early and late hepatocellular carcinoma recurrence.预测早期和晚期肝细胞癌复发的因素。
World J Gastroenterol. 2023 Feb 28;29(8):1243-1260. doi: 10.3748/wjg.v29.i8.1243.
4
Updating the Clinical Application of Blood Biomarkers and Their Algorithms in the Diagnosis and Surveillance of Hepatocellular Carcinoma: A Critical Review.更新血液生物标志物及其算法在肝细胞癌诊断和监测中的临床应用：批判性评价。
Int J Mol Sci. 2023 Feb 21;24(5):4286. doi: 10.3390/ijms24054286.
5
SLC27A5 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by downregulating glutathione reductase.SLC27A5 通过下调谷胱甘肽还原酶促进索拉非尼诱导的肝细胞癌铁死亡。
Cell Death Dis. 2023 Jan 12;14(1):22. doi: 10.1038/s41419-023-05558-w.
6
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7
Tracing the Anti-cancer Mechanism of Pleurotus osteratus by the Integrative Approach of Network Pharmacology and Experimental Studies.通过网络药理学和实验研究的综合方法探究糙皮侧耳的抗癌机制。
Appl Biochem Biotechnol. 2023 Jan;195(1):152-171. doi: 10.1007/s12010-022-04111-3. Epub 2022 Sep 6.
8
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Cancer Res. 2022 Oct 17;82(20):3845-3857. doi: 10.1158/0008-5472.CAN-21-4140.
9
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Cells. 2022 Aug 22;11(16):2610. doi: 10.3390/cells11162610.
10
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Nat Rev Gastroenterol Hepatol. 2022 Oct;19(10):670-681. doi: 10.1038/s41575-022-00620-y. Epub 2022 Jun 8.