Work

Exploring the interplay between EBV and autophagy-related gene expression patterns in nasopharyngeal carcinoma

Year: 2025

Type: article

Abstract: 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. Results: 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.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2025.1588921