Fatma Shaker

Egypt

piRNA-823 and Its Downstream Targets as a Potential Biomarker and Therapeutic Axis in Ovarian Cancer: Integrative Computational and Clinical Insights

Fatma H. Shaker1, Eman F. Sanad1, Nader M. Ibrahim2, Hesham Elghazaly3, Shih-Min Hsia4,5, Nadia M. Hamdy1,6

1. Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, 11566, Cairo, Egypt.
2. Department of Gynecology and Obstetrics, Faculty of Medicine, Ain Shams University, 11566, Cairo, Egypt.
3. Department of Clinical Oncology, Faculty of Medicine, Ain Shams University, 11566, Cairo, Egypt.
4. School of Food and Safety, Nutrition Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei 110301, Taiwan.
5. Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 110301, Taiwan.
6. The National Committee of Toxicology and Pharmacology Member, ASRT-Egypt, 11566, Cairo, Egypt.

Abstract

Background

Ovarian cancer (OC) is the most lethal gynecologic malignancy, with most patients diagnosed at advanced stages experiencing relapse and chemoresistance, leading to poor survival outcomes. P-element-induced wimpy testis (PIWI)-interacting (piRNAs) have emerged as critical regulators of gene expression and tumor biology. Here, we investigated the clinical significance of piRNA-823 and its regulatory axis involving PIWIL1, DNA methyltransferase 3B (DNMT3B), and E-cadherin (CDH1) in OC.

Methods

This study integrated clinical and computational analyses to investigate the expression and functional relevance of piR-823 and its associated PIWIL1/DNMT3B/CDH1 axis in OC. Expression profiling was performed using qPCR on OC and normal ovarian tissues, followed by correlation, regression, and ROC analyses. Public databases, including GEPIA, Enricher, and MethBank, were explored to validate gene expression, methylation status, and pathway enrichment.

Results

Expression analysis revealed that piRNA-823, PIWIL1, and DNMT3B were significantly upregulated in OC tissues and positively correlated with adverse clinicopathological features, including tumor grade, FIGO stage, lymph node metastasis, and ascites. Conversely, CDH1 expression was significantly downregulated, while N-cadherin (CDH2), OCT4, and NANOG were upregulated, consistent with epithelial–mesenchymal transition (EMT) and stemness activation. ROC curve analysis revealed that piRNA-823 had strong diagnostic performance for distinguishing OC tissues from normal controls. piRNA-823 expression positively correlated with PIWIL1 and DNMT3B, while DNMT3B inversely correlated with CDH1. In silico enrichment analyses supported piR-823 and DNMT3B-mediated EMT/stemness pathways.

Conclusions

Our study suggests a potential piRNA-823/PIWIL1/DNMT3B/CDH1 epigenetic axis in OC that drives EMT and cancer stemness, contributing to OC aggressiveness. These findings highlight piRNA-823 as a potential diagnostic, prognostic, and therapeutic target in OC.