Lymph node metastasis (LNM) and lymphatic vasculature space infiltration (LVSI) in cervical cancer patients indicate a poor prognosis, but satisfactory methods for diagnosing these phenotypes are lacking. This study aimed to find new effective plasma biomarkers of LNM and LVSI as well as possible mechanisms underlying LNM and LVSI through data-independent acquisition (DIA) proteome sequencing. A total of 20 cervical cancer plasma samples, including 7 LNM-/LVSI-(NC), 4 LNM-/LVSI + (LVSI) and 9 LNM + /LVSI + (LNM) samples from a cohort, were subjected to DIA to identify differentially expressed proteins (DEPs) for LVSI and LNM. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for DEP functional annotation. Protein–protein interaction (PPI) and weighted gene coexpression network analysis (WGCNA) were used to detect new effective plasma biomarkers and possible mechanisms. A total of 79 DEPs were identified in the cohort. GO and KEGG analyses showed that DEPs were mainly enriched in the complement and coagulation pathway, lipid and atherosclerosis pathway, HIF-1 signal transduction pathway and phagosome and autophagy. WGCNA showed that the enrichment of the green module differed greatly between groups. Six interesting core DEPs (SPARC, HPX, VCAM1, TFRC, ERN1 and APMAP) were confirmed to be potential plasma diagnostic markers for LVSI and LNM in cervical cancer patients. Proteomic signatures developed in this study reflected the potential plasma diagnostic markers and new possible pathogenesis mechanisms in the LVSI and LNM of cervical cancer.

中文翻译：

---

宫颈癌淋巴结转移的新机制和生物标志物：血浆蛋白质组学的反思

宫颈癌患者的淋巴结转移（LNM）和淋巴管间隙浸润（LVSI）表明预后不良，但缺乏令人满意的诊断这些表型的方法。本研究旨在通过数据独立采集（DIA）蛋白质组测序寻找 LNM 和 LVSI 的新有效血浆生物标志物以及 LNM 和 LVSI 的可能机制。总共 20 份宫颈癌血浆样本，包括来自队列的 7 份 LNM-/LVSI-(NC)、4 份 LNM-/LVSI + (LVSI) 和 9 份 LNM + /LVSI + (LNM) 样本，进行 DIA 鉴定LVSI 和 LNM 的差异表达蛋白 (DEP)。随后，进行基因本体论（GO）和京都基因和基因组百科全书（KEGG）分析以进行DEP功能注释。蛋白质-蛋白质相互作用（PPI）和加权基因共表达网络分析（WGCNA）用于检测新的有效血浆生物标志物和可能的机制。该队列中总共识别出 79 个 DEP。GO和KEGG分析显示DEPs主要富集于补体和凝血途径、脂质和动脉粥样硬化途径、HIF-1信号转导途径以及吞噬体和自噬。WGCNA 显示绿色模块的富集程度在各组之间差异很大。六个有趣的核心 DEP（SPARC、HPX、VCAM1、TFRC、ERN1 和 APMAP）被证实是宫颈癌患者 LVSI 和 LNM 的潜在血浆诊断标志物。本研究中开发的蛋白质组特征反映了宫颈癌 LVSI 和 LNM 中潜在的血浆诊断标志物和新的可能发病机制。