ORIGINAL RESEARCH article
Front. Oncol.
Sec. Head and Neck Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1588921
This article is part of the Research TopicAutophagy in Solid Tumors and Inflammation: Mechanisms and TherapiesView all articles
Exploring the Interplay Between EBV and Autophagy-Related Gene Expression Patterns in Nasopharyngeal Carcinoma
Provisionally accepted
Abdullah E. Alanazi1
Dr. Maaweya Awadalla2
Amani Alowaini3Saad Alamri2Doaa Ali AlGhamdi2
Alyaa Saher4
Mohamed A. M. Ali5
Bandar Alosaimi2*- 1Saudi Food and Drug Authority (SFDA), Riyadh, Saudi Arabia
- 2King Fahd Medical City, Riyadh, Saudi Arabia
- 3Prince Sultan Military Medical City, As Sulimaniyah, Riyadh, Saudi Arabia
- 4Ain Shams University, Cairo, Cairo, Egypt
- 5Imam Muhammad ibn Saud Islamic University, Riyadh, Saudi Arabia
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Introduction/Aim: While components of the autophagy pathway have been linked to cancer prognosis, their relationship with clinical outcomes remains unclear. This study investigates the expression levels of autophagy-related genes (ATGs) at both mRNA and protein levels in nasopharyngeal carcinoma (NPC) and their association with Epstein-Barr virus (EBV) infection, clinicopathological characteristics, and clinical outcomes.Material and Methods: Thirty-five formalin-fixed, paraffin-embedded (FFPE) tissue specimens from NPC patients and five non-cancerous nasopharyngeal mucosa control samples were analyzed. Quantitative PCR (qPCR) was used to assess the mRNA levels of nine ATGs, while protein expression was evaluated by immunohistochemistry.The results showed that ATG3, ATG4D, ATG4C, ATG4A, ATG2B, and ATG5 expression were significantly higher in EBV-positive NPC, suggesting a notable role of EBV in modulating these genes. Expression of ATG3 and ATG4C proteins was significantly more frequent in EBV-positive NPC patients compared to EBV-negative patients, with a strong correlation between expression of ATG3 or ATG4C and EBV positivity (P = 0.002 for both proteins). Elevated ATG4B and ATG4D expression was significantly associated with reduced distant metastasis in NPC patients (P = 0.019) and within the EBV-positive subgroup (P = 0.014).Reduced ATG4D mRNA levels were also correlated with higher metastasis rates and shorter distant metastasis-free survival (DMFS), highlighting a potential association of ATG4D with DMFS.Conclusions: Overall, these findings emphasize the importance of assessing autophagy-related gene expression as a valuable tool for predicting clinical outcomes in NPC and underscore the need for further research to validate these results and explore therapeutic implications.
Keywords: Autophagy, Epstein-Barr virus, nasopharyngeal carcinoma, prognostic biomarker, clinical outcome
Received: 14 Mar 2025; Accepted: 05 Jun 2025.
Copyright: © 2025 Alanazi, Awadalla, Alowaini, Alamri, AlGhamdi, Saher, Ali and Alosaimi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bandar Alosaimi, King Fahd Medical City, Riyadh, Saudi Arabia
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