摩洛哥亚群人群鼻咽癌的蛋白质组学分析

鼻咽癌（NPC）是一种头颈部特殊的癌症，主要在东南亚和北非地区高发。尽管对环境和遗传因素进行了广泛分析，但关于其蛋白质组的研究甚少。对福尔马林固定包埋（FFPE）组织的蛋白质组学分析能提供宝贵的蛋白表达和分子特征信息，有助于加深对疾病的理解及生物标志物的发现。到目前为止，关于NPC的蛋白质组学研究极少，且未有针对来自摩洛哥和北非患者的研究。本研究采用无标记液相色谱-串联质谱（LC-MS/MS）技术，对来自摩洛哥及北非的41例NPC肿瘤样本的FFPE组织进行了蛋白质组分析。利用MaxQuant 2.4.2.0软件对这些样本与21名健康对照的蛋白质组数据进行了比对分析。通过R软件中的MSstats包进行了差异表达分析，利用DAVID工具进行了基因本体（GO）和京都基因与基因组百科全书（KEGG）功能注释。共鉴定出3341个蛋白，揭示了三个主要的簇和五个具有预后意义的差异表达蛋白（DEPs）。从蛋白质组角度探讨了NPC的性别差异，发现男性与女性之间有59个DEPs，免疫反应和基因表达相关的术语显著富集。此外，早期和晚期NPC患者之间观察到26个DEPs，主要包括上调的IGHA、IGKC和VAT1，提示免疫反应的差异。在全部数据集中，共定量了6532个蛋白，其中观察到1507个差异表达蛋白。GO和KEGG分析显示这些DEPs与细胞活性增强、细胞增殖和存活相关的途径富集，PI3K、MAPK、RAC1、BCL2和PPIA等蛋白在肿瘤组织与健康对照中表现出过表达。EBV病毒感染路径也被富集，其潜在基因如LMP1和LMP2激活多个蛋白及信号通路，包括NF-κB、MAPK和JAK-STAT途径。我们的研究首次揭示了摩洛哥人群中NPC的蛋白质组景观，为潜在生物标志物的发现提供基础，未来仍需深入研究以促进早期诊断和治疗策略的发展。

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.