鼻咽癌（NPC）是一种独特的头颈部癌症，在东南亚和北非非常流行。尽管已经对环境和遗传因素进行了广泛的分析，但人们对这种疾病的蛋白质组知之甚少。对福尔马林固定石蜡包埋 (FFPE) 组织进行蛋白质组学分析可以提供有关蛋白质表达和分子模式的宝贵信息，从而增进我们对疾病的了解和生物标志物的发现。迄今为止，进行的鼻咽癌蛋白质组学研究很少，且没有针对摩洛哥和北非患者的研究。使用无标记液相色谱-串联质谱 (LC-MS/MS) 对 FFPE 组织样本进行蛋白质组分析来自摩洛哥和北非起源的 41 个 NPC 肿瘤样本队列。使用 MaxQuant 2.4.2.0 与 21 名健康对照者一起分析了该队列的 LC-MS/MS 数据。使用 R 中的 MSstats 软件包进行差异表达分析。使用 DAVID 生物信息学工具进行基因本体论 (GO) 和京都基因和基因组百科全书 (KEGG) 功能注释。在我们的鼻咽癌病例中鉴定出 3341 个蛋白质，揭示了三个主要集群和五个具有预后意义的 DEP。从蛋白质组学的角度研究了NPC的性别差异，其中男性和女性之间发现了59个DEP，其中与免疫反应和基因表达相关的术语显着丰富。此外，在早期和晚期 NPC 患者之间观察到 26 个 DEP，其中有一个与免疫反应相关的显着簇，表明 IGHA、IGKC 和 VAT1 等 DEP 上调。在这两个数据集中，对 NPC 患者和健康对照之间的 6532 种蛋白质进行了定量。其中，观察到1507个差异表达蛋白（DEP）。 GO 和 KEGG 通路分析显示与细胞活性增加、细胞增殖和存活相关的 DEP 术语丰富。研究发现，PI3K 和 MAPK 蛋白以及 RAC1、BCL2 和 PPIA 在癌症组织和健康对照之间过度表达。 EBV 感染也是富集途径之一，涉及其 LMP1 和 LMP2 等潜在基因，这些基因激活多种蛋白质和信号通路，包括 NF-Kappa B、MAPK 和 JAK-STAT 通路。我们的研究结果首次揭示了 NPC 的蛋白质组学景观在摩洛哥人口中。这些研究还可以为识别潜在的生物标志物提供基础。仍需要进一步的研究来帮助开发摩洛哥和北非人群鼻咽癌早期诊断和治疗的工具。

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.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.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.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.