Exploring P62/SQSTM1 and Nrf2 as predictors of chemoresistance in ovarian cancer: An <i>in vitro</i> and clinical analysis

Ovarian cancer (OC) remains a major cause of female cancer mortality, with chemoresistance impeding effective treatment. This study investigated the expression of p62/SQSTM1 and Nrf2 in chemoresistant versus chemosensitive OC cell lines and patient tissues. Using quantitative reverse transcription PCR, Western blotting, and immunohistochemistry, we found co-upregulation of p62 and Nrf2 proteins in chemoresistant samples. Proliferation assays revealed that higher p62 expression correlated with reduced cisplatin sensitivity. Sanger sequencing detected synonymous p62 variants in exon 6, with no functional impact. Immunohistochemical scoring showed significantly higher p62 and Nrf2 levels in chemoresistant patients compared to remission and sensitive groups. A strong correlation was observed between p62 expression and cisplatin IC50 values. These findings support the role of the p62/Nrf2 axis in OC chemoresistance and highlight their potential as predictive biomarkers and therapeutic targets. Future studies are warranted to explore targeted interventions that disrupt this pathway to enhance treatment response in OC.