Reffai Ayman, Hori Michelle, Adusumilli Ravali, Bermudez Abel, Haddad Houssam, Tawfiq Nezha, Pitteri Sharon, Bennani Mechita Mohcine, Mallick Parag
Canary Center for Cancer Early Detection, School of Medicine, Stanford University, Stanford, CA 94305, USA.
Intelligent Automation and BioMed Genomics Laboratory, Biology Department, Faculty of Sciences and Techniques of Tangier, Abdelmalek Essaadi University-Tetouan, Tangier 90000, Morocco.
Int J Mol Sci. 2025 Jun 16;26(12):5771. doi: 10.3390/ijms26125771.
Nasopharyngeal carcinoma (NPC) is a multifactorial disease mainly affecting the Southeast Asian and North African populations. Critically, there is a dearth of available circulating biomarkers for NPC. Additionally, as of this writing, there have been no prior plasma proteomics studies on NPC in the Moroccan population. Accordingly, there has been no integrated analysis of tumor and plasma for NPC in the Moroccan sub-population. Label-free proteomics analysis was conducted on 25 samples of Moroccan origin (10 NPC samples and 15 healthy control samples). Each sample was depleted of albumin, fractionated into eight fractions, and then analyzed using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). A total of 291 proteins and 2702 unique peptides were identified across all samples. In total, 16 proteins were differentially expressed (DEPs) between NPC cases and healthy individuals. Of these, three showed prognostic significance, while four demonstrated diagnostic potential. A pathway analysis showed significantly enriched terms related to the immune response and chronic inflammation, revealing acute-phase proteins as differentially expressed. The investigation of patients with early and advanced stages of NPC revealed two DEPs, while four additional DEPs were identified across the three defined clusters of NPC. Across all comparisons, DEPs, such as H2A, IGHG2, SERPINA3, SAA1, CRP, PIGR, and APOA2, have shown potential as biomarkers for NPC, with several being identified for the first time. We additionally compared the plasma proteomic profile of NPC with the tumor proteomic profile, highlighting that deeper proteomics analysis of plasma may be required to quantify additional putative biomarkers that may be shed from the tumor into the blood. Our research presents the first plasma proteomic profile of NPC in Morocco and North Africa, identifying proteins that might ultimately have diagnostic and prognostic potential.
鼻咽癌(NPC)是一种多因素疾病,主要影响东南亚和北非人群。关键的是,目前缺乏可用于鼻咽癌的循环生物标志物。此外,截至撰写本文时,尚未有针对摩洛哥人群鼻咽癌的血浆蛋白质组学研究。因此,尚未对摩洛哥亚人群中的鼻咽癌进行肿瘤与血浆的综合分析。对25份摩洛哥来源的样本(10份鼻咽癌样本和15份健康对照样本)进行了无标记蛋白质组学分析。每个样本去除白蛋白后,分馏为八个组分,然后使用液相色谱 - 串联质谱(LC-MS/MS)进行分析。在所有样本中总共鉴定出291种蛋白质和2702种独特肽段。总体而言,鼻咽癌病例与健康个体之间有16种蛋白质差异表达(DEPs)。其中,三种显示出预后意义,四种具有诊断潜力。通路分析显示与免疫反应和慢性炎症相关的术语显著富集,揭示急性期蛋白为差异表达。对鼻咽癌早期和晚期患者的研究发现了两种DEPs,而在鼻咽癌的三个定义簇中又鉴定出另外四种DEPs。在所有比较中,诸如H2A、IGHG2、SERPINA3、SAA1、CRP、PIGR和APOA2等DEPs已显示出作为鼻咽癌生物标志物的潜力,其中几种是首次被鉴定出来。我们还比较了鼻咽癌的血浆蛋白质组图谱与肿瘤蛋白质组图谱,强调可能需要对血浆进行更深入的蛋白质组学分析,以量化可能从肿瘤释放到血液中的其他假定生物标志物。我们的研究展示了摩洛哥和北非地区鼻咽癌的首个血浆蛋白质组图谱,鉴定出了最终可能具有诊断和预后潜力的蛋白质。