宫颈癌淋巴结转移的新机制和生物标志物:来自血浆蛋白质组学的思考。
New mechanisms and biomarkers of lymph node metastasis in cervical cancer: reflections from plasma proteomics.
发表日期:2023 Sep 09
作者:
Sai Han, Xiaoli Liu, Shuang Ju, Wendi Mu, Gulijinaiti Abulikemu, Qianwei Zhen, Jiaqi Yang, Jingjing Zhang, Yi Li, Hongli Liu, Qian Chen, Baoxia Cui, Shuxia Wu, Youzhong Zhang
来源:
GENES & DEVELOPMENT
摘要:
淋巴结转移(LNM)和淋巴血管间隙浸润(LVSI)在宫颈癌患者中预示着不良预后,但缺乏满意的诊断这些表型的方法。本研究旨在通过数据无偏采集(DIA)蛋白组测序,寻找LNM和LVSI的新有效血浆生物标志物,并探讨LNM和LVSI的潜在机制。对20个宫颈癌患者的血浆样本进行DIA,包括7个LNM-/LVSI-(NC)、4个LNM-/LVSI+(LVSI)和9个LNM+ /LVSI+(LNM)样本,以鉴定LVSI和LNM的差异表达蛋白(DEPs)。随后,进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)分析,对DEP进行功能注释。利用蛋白质相互作用(PPI)和加权基因共表达网络分析(WGCNA)来检测新的有效血浆生物标志物和可能的机制。在这个队列中共鉴定出79个DEPs。GO和KEGG分析显示,DEPs主要富集在补体和凝血通路、脂质和动脉硬化通路、HIF-1信号传导通路、吞噬体和自噬中。WGCNA显示,绿色模块的富集在各组之间有很大差异。确认了6个有趣的核心DEP(SPARC、HPX、VCAM1、TFRC、ERN1和APMAP)作为宫颈癌患者LVSI和LNM的潜在血浆诊断标志物。本研究开发的蛋白质标志物反映了宫颈癌LVSI和LNM的潜在血浆诊断标志物和新的可能致病机制。© 2023年。BioMed Central Ltd.,Springer Nature的一部分。
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.© 2023. BioMed Central Ltd., part of Springer Nature.