摩洛哥亚群中鼻咽癌的蛋白质组学分析
A Proteomic Analysis of Nasopharyngeal Carcinoma in a Moroccan Subpopulation
影响因子:4.40000
分区:医学3区 / 肿瘤学3区
发表日期:2024 Sep 26
作者:
Ayman Reffai, Michelle Hori, Ravali Adusumilli, Abel Bermudez, Abdelilah Bouzoubaa, Sharon Pitteri, Mohcine Bennani Mechita, Parag Mallick
摘要
鼻咽癌(NPC)是头颈的一种独特的癌症,在东南亚和北非高度普遍。尽管已经对环境和遗传贡献者进行了广泛的分析,但对这种疾病的蛋白质组知之甚少。对福尔马林固定石蜡包含(FFPE)组织的蛋白质组学分析可以提供有关蛋白质表达和分子模式的有价值的信息,以增强我们对疾病的理解和生物标志物发现。迄今为止,很少进行NPC蛋白质组学研究,并且没有针对摩洛哥和北非的患者进行。无标签的液态色谱串联量质谱法(LC-MS/MS)用于对来自41 NPC Tumor of Morocco和North Africemape的组成的FFPE组织样品进行FFPE组织样品的蛋白质组学分析。使用Maxquant 2.4.2.0分析了该队列中的LC-MS/MS数据。使用R.基因本体论(GO)中的MSSTATS软件包进行了差异表达分析,并使用David BioInformic Tool进行了基因和基因组(KEGG)功能注释。3341在我们的NPC病例中识别出三个主要的簇和五个Deps compantics compantics。从蛋白质组学的角度研究了NPC的性别差异,在男性和女性之间发现59个DEP,与免疫反应和基因表达相关的术语显着富集。此外,在NPC的早期和晚期阶段的患者之间观察到26个DEP,与免疫反应相关的显着簇,这意味着上调的DEP,例如IGHA,IGKC和VAT1。在两个数据集中,NPC患者和健康对照组之间量化了6532个蛋白质。其中,观察到1507种差异表达的蛋白质(DEP)。 GO和KEGG途径分析表明,与细胞活性,细胞增殖和存活率增加有关的DEP的丰富术语。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表达。 EBV感染也是富含的途径之一,它涉及其潜在基因(如LMP1和LMP2),它激活了几种蛋白质和信号通路,包括NF-KAPPA B,MAPK和JAK-STAT途径。在摩洛哥群岛中,NPC的蛋白质组学景观揭示了NPC的蛋白质组学景观。这些研究还可以为识别潜在的生物标志物提供基础。仍然需要进一步的研究来帮助开发摩洛哥和北非人口的NPC早期诊断和治疗工具。
Abstract
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.