2. Academic Validation
  3. PNP as a Metabolic and Prognostic Driver of Breast Cancer Aggressiveness: Insights from Patient Tissue and Cell Models

PNP as a Metabolic and Prognostic Driver of Breast Cancer Aggressiveness: Insights from Patient Tissue and Cell Models

  • Oncol Res. 2025 Dec 30;34(1):13. doi: 10.32604/or.2025.070808.
Sarra B Shakartalla 1 2 3,  Iman M Talaat 1 2 4,  Nival Ali 1,  Shahenaz S Salih 1 5,  Zainab M Al Shareef 1 2,  Noura Alkhayyal 6,  Riyad Bendardaf 2 7,  Sameh S M Soliman 1 8
Affiliations

Affiliations

  • 1 Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, 27272, United Arab Emirates.
  • 2 College of Medicine, University of Sharjah, Sharjah, 27272, United Arab Emirates.
  • 3 Faculty of Pharmacy, University of Gezira, Wadmedani, 21111, Sudan.
  • 4 Faculty of Medicine, Alexandria University, Alexandria, 21131, Egypt.
  • 5 College of Medical Laboratory Sciences, Sudan University of Science and Technology, Khartoum, 11111, Sudan.
  • 6 Histopathology and Laboratory Medicine Department, University Hospital Sharjah, Sharjah, 72772, United Arab Emirates.
  • 7 Medical Oncology Unit, University Hospital Sharjah, Sharjah, 72772, United Arab Emirates.
  • 8 College of Pharmacy, University of Sharjah, Sharjah, 27272, United Arab Emirates.
PMID: 41502507 DOI: 10.32604/or.2025.070808
Abstract

Objectives: Breast Cancer (BC) is the leading cause of cancer-related mortality in women, largely due to metastasis. This study aims to explore the role of purine nucleoside Phosphorylase (PNP), a key enzyme in purine metabolism, in the aggressiveness and metastatic behavior of BC.

Methods: A comprehensive analysis was performed using in silico transcriptomic data (n = 2509 patients), immunohistochemical profiling of BC tissues (n = 103), and validation through western blotting in multiple BC cell lines. Gene expression and survival analyses were conducted using Tumor Immune Estimation Resource (TIMER), Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the cBioPortal for Cancer genomics (cBioPortal) platforms. Correlations between PNP and key epithelial-mesenchymal transition (EMT) markers, molecular subtypes, tumor grades, and stages were examined.

Results: PNP was significantly overexpressed in human epidermal growth factor receptor 2 (HER-2)-positive and triple-negative BCs compared to luminal subtypes. High PNP levels were strongly associated with advanced BC stages, high-grade tumors, EMT phenotypes, and poor overall survival. Notably, HER-2 inhibition suppressed PNP expression, while PNP gene silencing induced HER-2 upregulation, revealing a reciprocal regulatory loop. Dual inhibition of PNP and HER-2 resulted in a significant reduction in cell viability compared to HER-2 inhibition alone.

Conclusion: Collectively, PNP emerges as a promising biomarker of BC aggressiveness and progression. Its reciprocal interaction with HER-2 underscores its potential as a therapeutic target. Dual targeting of PNP and HER-2 may offer a novel strategy for improving outcomes in aggressive BC subtypes.

Keywords

Purine nucleoside phosphorylase; breast cancer; hypoxanthine; metastasis.

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