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BRIEF RESEARCH REPORT article

Front. Genet.

Sec. Cancer Genetics and Oncogenomics

Volume 16 - 2025 | doi: 10.3389/fgene.2025.1611805

This article is part of the Research TopicLung Adenocarcinoma: From Genomics to Immunotherapy, Volume IIView all 18 articles

Identification of Oncofetal PIWI-interacting RNAs as Potential Prognostic Biomarkers in Non-Small Cell Lung Cancer

Provisionally accepted
Michelle E PewarchukMichelle E Pewarchuk1,2*Vanessa G. P. SouzaVanessa G. P. Souza1David E CohnDavid E Cohn1,2Nikita TelkarNikita Telkar1,3,4Greg L StewartGreg L Stewart1,2Katya H BénardKatya H Bénard1,2Patricia P ReisPatricia P Reis5Victor D MartinezVictor D Martinez6,7Wendy P RobinsonWendy P Robinson3,4Wan L LamWan L Lam1,2
  • 1BC Cancer Research Institute, Faculty of Medicine, University of British Columbia, Vancouver, Canada
  • 2Interdisciplinary Oncology Program, University of British Columbia, Vancouver, British Columbia, Canada
  • 3Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  • 4BC Children's Hospital Research Institute, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
  • 5Department of Surgery and Orthopedics, Faculty of Medicine, Sao Paulo State University (UNESP), Botucatu, Brazil
  • 6Department of Pathology and Laboratory Medicine, IWK Health Centre, Halifax, Canada
  • 7Department of Pathology, Dalhousie University, Halifax, Canada

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Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for the majority of these cases. Despite advancements in targeted therapies, early detection remains a significant challenge, highlighting the need for novel biomarkers. This study investigates the role of PIWI-interacting RNAs (piRNAs) in lung cancer, specifically focusing on their potential as oncofetal biomarkers in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two most common histological subtypes of NSCLC. We hypothesize that piRNAs exhibit oncofetal expression patterns and may contribute to lung cancer development. Through bioinformatics analysis, we identified distinct piRNA profiles in non-neoplastic, malignant, and fetal lung tissues. Among these, 37 piRNAs in LUAD and 46 piRNAs in LUSC displayed oncofetal expression, meaning they were present in tumor tissues but absent in adjacent normal lung tissue. These oncofetal piRNAs showed significant prognostic value in both LUAD and LUSC cohorts, with a specific signature of eight oncofetal piRNAs predicting high-risk patients in LUAD. We validated the robustness of this signature in a separate in-house cohort, which underscores its potential as a prognostic biomarker. Our findings suggest that oncofetal piRNAs could offer new diagnostic and therapeutic opportunities, particularly for early detection.

Keywords: lung cancer, PIWI-interacting RNAs, oncofetal biomarkers, Lung Adenocarcinoma, Lung squamous cell carcinoma

Received: 14 Apr 2025; Accepted: 01 Aug 2025.

Copyright: © 2025 Pewarchuk, Souza, Cohn, Telkar, Stewart, Bénard, Reis, Martinez, Robinson and Lam. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Michelle E Pewarchuk, BC Cancer Research Institute, Faculty of Medicine, University of British Columbia, Vancouver, Canada

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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