Proteomics-Based Mapping of the Lymph Node Metastasis Landscape in Cervical Cancer

IF 3.6 2区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

Journal of Proteome Research Pub Date : 2025-09-11 DOI:10.1021/acs.jproteome.5c00570

Yiping Hao, , , Qingqing Liu, , , Bingyu Wang, , , Wenjing Zhang, , , Xinlin Jiao, , , Teng Zhang*, , and , Baoxia Cui*,

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引用次数: 0

Abstract

Lymph node metastasis (LNM) in cervical cancer is a critical determinant of the disease progression and prognosis. Elucidating its molecular mechanisms and identifying specific biomarkers are crucial for optimizing treatment. DIA-based quantitative proteomic sequencing was conducted on 49 cervical cancer patients. We screened differentially expressed proteins and performed functional enrichment, pathway scoring, time-series analysis, protein interaction studies, and integrated proteomic and TCGA transcriptomic data to identify biomarkers. 56 genes showed consistent expression trends, with 2 upregulated (SERPINB5, FABP5) and 54 downregulated (including ZNF512). Novel findings include activation of unsaturated fatty acid/steroid biosynthesis and inhibition of cell junction pathways during progression. Lymphovascular space invasion (LVSI) precedes LNM, but a subset of LNM cases lacks LVSI and exhibits a unique cholesterol metabolism activation. SERPINB5, FABP5, and ZNF512 were validated as potential prognostic and LNM-predictive biomarkers. DIA proteomics characterized cervical cancer lymph node metastasis, revealing molecular changes and potential biomarkers and offering new insights into its biological mechanisms.

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基于蛋白质组学的宫颈癌淋巴结转移图谱研究。

宫颈癌的淋巴结转移（LNM）是疾病进展和预后的关键决定因素。阐明其分子机制和识别特异性生物标志物对优化治疗至关重要。对49例宫颈癌患者进行了基于dia的定量蛋白质组学测序。我们筛选了差异表达蛋白，并进行了功能富集、途径评分、时间序列分析、蛋白质相互作用研究，并整合了蛋白质组学和TCGA转录组学数据，以确定生物标志物。56个基因表达趋势一致，其中2个基因表达上调（SERPINB5、FABP5）， 54个基因表达下调（包括ZNF512）。新的发现包括激活不饱和脂肪酸/类固醇生物合成和抑制细胞连接途径在进展。淋巴血管间隙侵袭（LVSI）先于LNM，但一小部分LNM病例缺乏LVSI，并表现出独特的胆固醇代谢激活。SERPINB5、FABP5和ZNF512被证实为潜在的预后和预测lnm的生物标志物。DIA蛋白质组学表征了宫颈癌淋巴结转移，揭示了其分子变化和潜在的生物标志物，并为其生物学机制提供了新的见解。

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来源期刊

Journal of Proteome Research 生物-生化研究方法

CiteScore

9.00

自引率

4.50%

发文量

251

审稿时长

3 months

期刊介绍： Journal of Proteome Research publishes content encompassing all aspects of global protein analysis and function, including the dynamic aspects of genomics, spatio-temporal proteomics, metabonomics and metabolomics, clinical and agricultural proteomics, as well as advances in methodology including bioinformatics. The theme and emphasis is on a multidisciplinary approach to the life sciences through the synergy between the different types of "omics".