Exploring P62/SQSTM1 and Nrf2 as predictors of chemoresistance in ovarian cancer: An in vitro and clinical analysis
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Khaldoon Alsamman 1 , Amani Y Owaidah 1 , Faisal Azam 2 , Miral Mashhour 2 , Kholoud Alwosaibai 2 , Ghaida A Aldossary 1 , Morouj H Althagafi 1 , Nesma A Ghazal 3 , Omar S El-Masry 1 *
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1 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University, Dammam, SAUDI ARABIA2 King Fahd Specialist Hospital, Dammam, SAUDI ARABIA3 Department of Biochemistry, Medical Research Institute, Alexandria, University of Alexandria, EGYPT* Corresponding Author

Abstract

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.

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Article Type: Original Article

ELECTRON J GEN MED, Volume 22, Issue 6, December 2025, Article No: em695

https://doi.org/10.29333/ejgm/17252

Publication date: 01 Nov 2025

Online publication date: 09 Oct 2025

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