基于DIA定量分析技术研究鼻咽癌根治后远处转移患者的血清蛋白质表达

Study on serum proteomics of nasopharyngeal carcinoma patients with distant metastasis after radical treatment by data independent acquisition

目的:研究鼻咽癌根治后远处转移(rM)和无转移组(CR)患者的血清蛋白质表达谱差异。方法:分别选取5例鼻咽癌根治后发生转移患者及5例无转移患者的血清样本,利用非数据依赖性采集(data-independent acquisition,DIA)质谱技术,比较两组患者的血清蛋白质表达谱,获取差异表达蛋白,并通过GO功能和KEGG通路分析方法对差异蛋白进行富集分析。结果:在所有待测血清样品中最终共鉴定到2 485个蛋白,经筛选共获得差异表达蛋白68个,其中转移组中上调表达蛋白61个,下调表达蛋白7个。富集分析表明差异表达蛋白在补体激活、免疫调控等生物学过程富集,与补体结合及多个酶活性等分子功能密切有关;主要在血液微粒、细胞外区域、细胞外间隙及细胞外泌体等细胞组分间发挥功能。涉及补体与凝血级联、肌动蛋白细胞骨架调控以及细胞凋亡等关键信号通路。结论:血清差异表达蛋白质可能与鼻咽癌转移密切相关,有望成为潜在的鼻咽癌转移预测指标和干预靶点。

Objective:To investigate the differences in serum protein expression profiles between NPC patients with distant metastasis(rM) and those without metastasis(CR) after radical treatment.Methods:Serum samples were collected from five NPC patients who developed metastasis after radical treatment,and other five samples from those without metastasis.Data-independent acquisition(DIA) was used to compare the serum protein expression profiles of the two groups of patients,and differentially expressed proteins were identified.Enrichment analysis of the differentially expressed proteins was performed using gene ontology(GO) functional and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analysis methods.Results:A total of 2 485 proteins were identified in all tested serum samples,and there were altogether 68 differentially expressed proteins were obtained through screening.Among them,61 were upregulated and 7 were downregulated in the metastatic group.Enrichment analysis showed that these differentially expressed proteins were mainly enriched in biological processes such as complement activation and immune regulation,and are closely related to molecular functions such as complement binding and multiple enzyme activities,and the cellular components such as blood particles,extracellular region,extracellular space and exosome.They were participated in key signal pathways such as complement and coagulation cascade,actin cytoskeleton regulation and cell apoptosis.Conclusion:Differentially expressed serum proteins may be closely related to NPC metastasis and have the potential to become potential prognostic indicators and intervention targets for metastatic NPC.