Scientific Research
About
Research Focus
Biomedicine and Health, Cellular and Molecular Biology, Omics (Genomics, Proteomics, transcriptomics, …), Bioinformatics, Longevity, Human Performance, Neuroscience, and Biotechnology.
Research profiles
My Academic Publications (First author)
2024
A Proteomic Analysis of Nasopharyngeal Carcinoma in a Moroccan Subpopulation- Cancers MDPI (Q1)
Ayman Reffai, Michelle Hori, Ravali Adusumilli, Abel Bermudez, Abdelilah Bouzoubaa, Sharon Piterri, Mohcine Bennani Mechita, and Parag Mallick
Abstract
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.
2021
Epidemiological Profile and Clinicopathological, Therapeutic, and Prognostic Characteristics of Nasopharyngeal Carcnioma in Northern Morocco- Cancer Control SAGE (Q2)
Ayman Reffai, Mohamed Mesmoudi, Touria Derkaoui, Naima Ghailani Nourouti, Amina Barakat, Nabila Sellal, Parag Mallick, and Mohcine Bennani Mechita
Abstract
Background: Nasopharyngeal carcinoma is a multifactorial disease mainly affecting the Asian and North African populations including Morocco. This study aimed to determine the epidemiological profile of nasopharyngeal carcinoma in Northern Morocco as well as its clinicopathological, therapeutic, and prognostic characteristics. Methods: 129 patients with nasopharyngeal carcinoma followed at the regional center of oncology of Tangier in the period between April 2017 and July 2019, and diagnosed elsewhere from March 2000 to February 2019, were included in this study. Statistical analysis of the data was realized using Statistical Package for the Social Sciences (SPSS) software. Results: Nasopharyngeal carcinoma (NPC) represented 5% of all cases with a median age of 50. The most affected age group was 40–54 years (41.1%). Of all patients, 65.9% were men and 34.1% were women with a sex ratio of 1.93 (Male/Female). Undifferentiated nasopharyngeal carcinomas were the most common histological type affecting 96.12% of patients. At diagnosis, the majority of patients (82.2%) had an advanced stage of NPC (III, VIa, b, c) including 5.4% of metastatic cases (IVc). Most cases (86%) had lymph node involvement with cervical mass being the most common clinical presentation. 81.4% of patients received radiotherapy combined with chemotherapy. Among these patients, 54.3% had concurrent radiochemotherapy preceded by induction chemotherapy. The 5-year overall survival (OS) was 86.8% for all patients. It represented 91.3% for early stages, 87.9% for locally advanced stages, and 57.1% for the metastatic stage significantly. The disease-free survival (DFS) at 5 years was 87.6% knowing that relapse occurred in 16 cases. Conclusion: Nasopharyngeal carcinoma is a particular disease with a late declaration. It is common in Morocco as is the case in other endemic areas with a high prevalence. Patients’ survival is significantly influenced by disease staging.
PhD Research Project
Summary
Nasopharyngeal carcinoma (NPC) is a multifactorial head and neck cancer, mainly affecting Asian and North African populations, including Morocco. Despite thorough analyses of environmental and genetic factors, few proteomics studies on NPC have been conducted, with none focused on Morocco or North Africa. Our PhD research aimed to explore the molecular profile of NPC through proteomics and identify its epidemiological and clinical characteristics in Morocco.
In this research, statistical analysis in R on Moroccan NPC patients revealed a notable sex disparity, with males at higher risk. The findings showed that most patients are diagnosed at advanced stages, confirming the late detection problem of NPC. Clinicopathological, therapeutic, and prognostic features were also highlighted. Moreover, Kaplan-Meier survival analysis in R showed that overall survival was significantly influenced by disease staging.
For both FFPE tissues and plasma, the proteomics analysis using Label-free Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) identified key differentially expressed proteins (DEPs) among NPC subtypes, patients with early and advanced stages, male and female patients, and between NPC cases and healthy controls. Bioinformatics analysis investigating these DEPs was carried out using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations. This pathway analysis revealed significantly enriched terms associated with cellular growth and proliferation, as well as an immune reaction and chronic inflammation. The Epstein-Barr virus infection pathway was also reported. Differential proteins such as PI3K, MAPK, RAC1, and BCL2, along with less-known proteins like VAT1, PRP8, and BID, were implicated in these pathways and associated with NPC. Notably, SERPINA3 and APOA2 were significant proteins identified in both FFPE tissues and plasma samples.
Our findings characterize the molecular landscape of NPC for the first time in Morocco and Africa, identifying potential biomarkers that may ultimately enhance early diagnosis, prognosis, and therapeutic approaches for NPC. This research also lays a foundation for future studies in this field of interest.
Keywords: nasopharyngeal carcinoma, molecular profile, proteomics, bioinformatics, differentially expressed proteins, biomarkers, epidemiology, survival, diagnosis, prognosis.
Other Research Publications
Research papers with my Lumiere mentees
The Role of Epstein-Barr Virus in the Pathogenesis of Nasopharyngeal Carcinoma (JHSS 2025)
Kristie Lu, Ayman Reffai
Nicotine’s Impact During Metabolism in The Liver, With Disease Pro-gression, As Well As Genetic Factors During Nicotine Metabolism (NHSJS 2024)
Soha Porwal, Ayman Reffai
Interesting Publications
Biomedical Research
Coordinated inheritance of extrachromosomal DNAs in cancer cells (Nature 2024)
DOI: https://doi-org.stanford.idm.oclc.org/10.1038/s41586-024-07861-8
Application of Artificial Intelligence to the Diagnosis and Therapy of Nasopharyngeal Carcinoma (Journal of Clinical Medicine, 2023)
DOI: 10.3390/jcm12093077
The complete sequence of a human genome (Science, 2022)
The Need for Multi-Omics Biomarker Signatures in Precision Medicine (International Journal of Molecular Sciences, 2019)
DOI: 10.3390/ijms20194781
Neuroscience
Circadian rhythms in neurodegenerative disorders (Nature Reviews, Neurology, 2022)
Health and Longevity
The effect of fasting or calorie restriction on autophagy induction: A review of the literature (Ageing Research Reviews, 2018)
https://doi.org/10.1016/j.arr.2018.08.004
