Decreased Expression Levels Of PIWIL2, PIWIL3 and PIWIL4 Are Associated with Poor Prognosis and Worse Survival in Bladder Cancer Patients

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Hammad G.; Magdy M.; Aboushousha T.; Safwat G.; Hemida E.; Elesaily K.; Mamdouh S.

Journal: Asian Pacific Journal of Cancer Prevention

Publisher: Asian Pacific Organization for Cancer Prevention

Publication Date: 1 July 2025

Volume / Issue: Volume 26 / Issue 7

Pages: 2467–2477

ISSN: 15137368

DOI: 10.31557/APJCP.2025.26.7.2467

Scopus: View on Scopus

PubMed: 40729068

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Hammad G., October University for Modern Sciences & Arts (MSA), Faculty of Biotechnology, Giza, Egypt; Magdy M., Department of Pathology, Theodor Bilharz Research Institute (TBRI), Giza, Egypt; Aboushousha T., Department of Pathology, Theodor Bilharz Research Institute (TBRI), Giza, Egypt; Safwat G., October University for Modern Sciences & Arts (MSA), Faculty of Biotechnology, Giza, Egypt; Hemida E., Department of Biochemistry, Obstetrics and Gynecology Hospital, Ain Shams University, Cairo, Egypt; Elesaily K., Urology Department, Theodor Bilharz Research Institute, Giza, Egypt; Mamdouh S., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt

Abstract

Background: Bladder cancer (BC) remains one of the most prevalent and recurrent malignancies worldwide. Identification of early biomarkers and prognostic indicators is vital for improving diagnostic accuracy and therapeutic outcomes. PIWI-interacting RNA pathway proteins (PIWILs), known regulators of gene silencing and genome stability, have emerged as potential biomarkers in various cancers. This study evaluates the expression patterns of PIWIL1–4 in BC patients and investigates their prognostic value. Methods: Tumor and adjacent tissues were collected from 220 BC patients, along with urine samples from both patients and 70 healthy controls. Total RNA was extracted, followed by cDNA synthesis and real-time PCR for PIWIL1–4. Protein expression of PIWIL2 was evaluated by immunohistochemistry. Clinical data, including staging and histopathological features, were analyzed. In silico analysis (cBioPortal, miRNet) was performed to assess PIWIL gene variants and miRNA associations. Receiver operating characteristic (ROC) curves, logistic regression, and survival analysis were conducted for diagnostic and prognostic assessments. Results: Expression of all four PIWILs was significantly downregulated in both tissue and urine samples of BC patients compared to controls (p < 0.001). ROC analysis showed high sensitivity and specificity for PIWILs in distinguishing BC from controls (AUC ≥ 0.927). Logistic regression confirmed their diagnostic and prognostic relevance (p < 0.001). PIWIL2, PIWIL3, and PIWIL4 were significantly associated with tumor recurrence (p ≤ 0.01), while all four PIWILs correlated with patient survival. Immunohistochemical analysis of PIWIL2 supported its expression relevance. In silico findings revealed a 7% structural variant frequency for PIWIL2 and functional associations with tumor suppressor miRNAs. Conclusion: PIWIL1–4, particularly PIWIL2, are significantly downregulated in BC and hold promise as non-invasive diagnostic and prognostic biomarkers. Their expression correlates with recurrence and survival, suggesting clinical utility for improving bladder cancer management. Further studies are recommended to validate these findings in larger cohorts. © This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International License.

Keywords

Bladder cancer (BC); diagnosis; PIWIL1; PIWIL2; PIWIL3; PIWIL4; qPCR; relative expression patterns; Aged; Argonaute Proteins; Biomarkers, Tumor; Case-Control Studies; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Prognosis; RNA-Binding Proteins; ROC Curve; Survival Rate; Urinary Bladder Neoplasms; argonaute protein; PIWIL2 protein, human; PIWIL3 protein, human; PIWIL4 protein, human; RNA binding protein; tumor marker; bladder tumor; case control study; follow up; gene expression regulation; genetics; human; metabolism; mortality; pathology; receiver operating characteristic

Citation Information

Scopus Citations: 1

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