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PCNA in Pan-Cancer: A Prognostic Biomarker Unveiled Through a Data-Driven, Multidimensional Analysis of
Depanshi Pandit1, Ravindranath Bilachi Sanganabasappa1, Amardeep Dhillon2
1Department of Biotechnology, Manipal Institute of Technology, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.
ACS Omega
|July 14, 2025
Summary
Proliferating cell nuclear antigen (PCNA) is crucial in DNA repair and cell growth. This pan-cancer study reveals PCNA
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Proliferating cell nuclear antigen (PCNA) is a key regulator of DNA metabolism, cell cycle, and genetic integrity.
- PCNA dysregulation is implicated in neoplastic proliferation, genomic instability, and impaired DNA repair.
- The pan-cancer relevance of PCNA in tumorigenesis, immune interactions, and therapeutic resistance is not fully understood.
Purpose of the Study:
- To conduct a comprehensive pan-cancer analysis of PCNA expression.
- To investigate the associations between PCNA and immunological, survival, genetic, functional, and drug sensitivity profiles.
- To explore PCNA's role in tumorigenesis, immune evasion, and therapeutic resistance across diverse cancer types.
Main Methods:
- Analysis of publicly available multiomics databases.
- Assessment of PCNA mRNA levels, genetic alterations (amplification, hypomethylation), and pathway associations (Wnt, Hippo, mTOR).
- Correlation analysis with tumor-infiltrating lymphocytes, immune checkpoints, chemokines, and drug sensitivity.
Main Results:
- PCNA mRNA levels are altered across various cancers and linked to Wnt, Hippo, and mTOR signaling pathways.
- Increased PCNA expression correlates with poor overall survival in specific cancers (ACC, CESC, LGG, THYM).
- PCNA upregulation is associated with altered immune microenvironments, including tumor-infiltrating lymphocytes and chemokines, and increased sensitivity to drugs like Navitoclax and Ciclopirox.
Conclusions:
- This study provides the first comprehensive pan-cancer analysis of PCNA, highlighting its prognostic significance and altered expression.
- Tumor-specific genetic alterations and the paradoxical immune microenvironment linked to PCNA suggest potential immune evasion mechanisms.
- PCNA's association with drug sensitivity offers potential therapeutic strategies, particularly with agents like Navitoclax and Ciclopirox.
