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

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.宫颈癌淋巴结转移（Lymph node metastasis, LNM）是影响疾病进展与预后的关键决定性因素。阐明其分子机制并筛选特异性生物标志物，对于优化临床治疗方案至关重要。本研究对49例宫颈癌患者开展了基于数据非依赖采集（Data Independent Acquisition, DIA）的定量蛋白质组测序分析：通过筛选差异表达蛋白，开展功能富集分析、通路评分、时序分析、蛋白质相互作用研究，并整合蛋白质组与癌症基因组图谱（The Cancer Genome Atlas, TCGA）转录组数据以筛选潜在生物标志物。最终共有56个基因呈现出一致的表达趋势，其中2个基因表达上调（SERPINB5、FABP5），54个基因表达下调（包含ZNF512）。本研究的新发现包括：在疾病进展过程中，不饱和脂肪酸/类固醇生物合成通路被激活，而细胞连接通路受到抑制。脉管癌栓（Lymphovascular space invasion, LVSI）通常先于淋巴结转移发生，但部分淋巴结转移病例并未出现脉管癌栓，且呈现出独特的胆固醇代谢激活特征。经验证，SERPINB5、FABP5与ZNF512可作为潜在的预后及淋巴结转移预测生物标志物。基于DIA的蛋白质组学分析系统解析了宫颈癌淋巴结转移的分子特征，揭示了其分子层面的变化与潜在生物标志物，为阐明该疾病的生物学机制提供了全新视角。