Background: Nasopharyngeal carcinoma (NPC) is a distinct cancer of the head and neck that is highly prevalent in Southeast Asia and North Africa. Though an extensive analysis of environmental and genetic contributors has been performed, very little is known about the proteome of this disease. A proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissues can provide valuable information on protein expression and molecular patterns for both increasing our understanding of the disease and for biomarker discovery. To date, very few NPC proteomic studies have been performed, and none focused on patients from Morocco and North Africa. Methods: Label-free Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) was used to perform a proteomic analysis of FFPE tissue samples from a cohort of 41 NPC tumor samples of Morocco and North Africa origins. The LC-MS/MS data from this cohort were analyzed alongside 21 healthy controls using MaxQuant 2.4.2.0. A differential expression analysis was performed using the MSstats package in R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations were carried out using the DAVID bioinformatic tool. Results: 3341 proteins were identified across our NPC cases, revealing three main clusters and five DEPs with prognostic significance. The sex disparity of NPC was investigated from a proteomic perspective in which 59 DEPs were found between males and females, with significantly enriched terms associated with the immune response and gene expression. Furthermore, 26 DEPs were observed between patients with early and advanced stages of NPC with a significant cluster related to the immune response, implicating up-regulated DEPs such as IGHA, IGKC, and VAT1. Across both datasets, 6532 proteins were quantified between NPC patients and healthy controls. Among them, 1507 differentially expressed proteins (DEPs) were observed. GO and KEGG pathway analyses showed enriched terms of DEPs related to increased cellular activity, cell proliferation, and survival. PI3K and MAPK proteins as well as RAC1 BCL2 and PPIA were found to be overexpressed between cancer tissues and healthy controls. EBV infection was also one of the enriched pathways implicating its latent genes like LMP1 and LMP2 that activate several proteins and signaling pathways including NF-Kappa B, MAPK, and JAK-STAT pathways. Conclusion: Our findings unveil the proteomic landscape of NPC for the first time in the Moroccan population. These studies additionally may provide a foundation for identifying potential biomarkers. Further research is still needed to help develop tools for the early diagnosis and treatment of NPC in Moroccan and North African populations.
背景：鼻咽癌是一种独特的头颈部癌症，在东南亚和北非地区高发。尽管已对环境与遗传因素进行了广泛分析，但对该疾病的蛋白质组学特征仍知之甚少。对福尔马林固定石蜡包埋组织进行蛋白质组学分析，可为蛋白质表达和分子模式提供重要信息，既能增进我们对疾病的理解，也有助于生物标志物的发现。迄今为止，针对鼻咽癌的蛋白质组学研究极少，且尚未有研究聚焦于摩洛哥及北非地区的患者。 方法：采用无标记液相色谱-串联质谱技术对41例源自摩洛哥及北非地区的鼻咽癌肿瘤FFPE组织样本进行蛋白质组学分析。使用MaxQuant 2.4.2.0软件将该队列的LC-MS/MS数据与21例健康对照样本进行联合分析。通过R语言中的MSstats软件包进行差异表达分析，并利用DAVID生物信息学工具进行基因本体论和京都基因与基因组百科全书功能注释。 结果：在鼻咽癌病例中共鉴定出3341种蛋白质，揭示了三个主要聚类和五种具有预后意义的差异表达蛋白。研究从蛋白质组学角度探讨了鼻咽癌的性别差异，发现男女性患者间存在59种差异表达蛋白，其中显著富集的功能条目与免疫应答和基因表达相关。此外，在早期与晚期鼻咽癌患者间观察到26种差异表达蛋白，其中与免疫应答相关的显著聚类提示IGHA、IGKC和VAT1等蛋白表达上调。在鼻咽癌患者与健康对照组的对比分析中，共定量检测到6532种蛋白质，其中1507种为差异表达蛋白。GO和KEGG通路分析显示，差异表达蛋白显著富集于细胞活性增强、细胞增殖和存活等相关功能条目。癌组织与健康对照相比，PI3K、MAPK蛋白以及RAC1、BCL2和PPIA均呈现过表达。EB病毒感染也是显著富集的通路之一，其潜伏基因LMP1和LMP2可激活包括NF-κB、MAPK和JAK-STAT在内的多种蛋白及信号通路。 结论：本研究首次揭示了摩洛哥人群鼻咽癌的蛋白质组学特征，为潜在生物标志物的鉴定提供了基础。仍需进一步研究以开发适用于摩洛哥及北非人群的鼻咽癌早期诊断和治疗工具。
A Proteomic Analysis of Nasopharyngeal Carcinoma in a Moroccan Subpopulation
肿瘤(癌症)患者之家