Work

Nuclear factor E2 p45-related factor (NRF2) and peroxiredoxin 6 tissular expression as prognostic biomarkers for advanced HPV-negative squamous cell carcinoma of the oropharynx

Year: 2025

Type: article

Abstract: • NRF2 and peroxiredoxin 6 are overexpressed in tumor tissue compared to healthy tissue prior to any treatment, suggesting their involvement in therapy resistance. • High tumoral expression of NRF2 or peroxiredoxin 6 are negative prognostic factors on survival outcomes in non-HPV-induced oropharyngeal SCC patient. • Associating peroxiredoxin 6 and NRF2 expression improves patient survival prediction. Non-HPV-induced squamous cell carcinomas (SCC) of the oropharynx have a poorer prognosis than HPV-induced cancers because they are more radio- and chemoresistant. Currently, no predictive biomarker exists for survival outcome in this type of tumor. NRF2 is a nuclear transcription factor that regulates the expression of cytoprotective genes, and peroxiredoxin 6 is one of the proteins regulated by NRF2. Both are potentially involved in the resistance to treatments as they play a central role in the response to oxidative stress. In a retrospective cohort study of 53 patients with advanced HPV-negative squamous cell carcinomas of the oropharynx, we studied the correlation between clinical characteristics, response to treatment (surgery + radiotherapy), patient survival, and the expression of NRF2 and peroxiredoxin 6 in pre-treatment tumor biopsies. We prepared Tissue Micro Arrays (TMA) before performing immunohistochemistry analyses. For a given patient, prior to any treatment, NRF2 and peroxiredoxin 6 are overexpressed in tumor tissue compared with healthy tissue. Moreover, patients with high NRF2 expression tended to have poorer progression-free survival ( p = 0,09). Patients with high expression of peroxiredoxin 6 had significantly worse progression-free survival and overall survival ( p = 0.015 and p < 0.01, respectively). The combination of high NRF2 and peroxiredoxin 6 expression was associated with even worse survival outcomes ( p < 0.01and p = 0.01, respectively). Elevated expression levels of peroxiredoxin 6, either alone or in combination with NRF2, are poor prognostic indicators for patient survival.

Source: Translational Oncology

DOI: 10.1016/j.tranon.2025.102595