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ORIGINAL RESEARCH article
Front. Oncol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1593281
This article is part of the Research TopicDecoding Tumor Drug Resistance: Machine Learning’s Role from Molecules to TreatmentView all 10 articles
PCDH1 Coordinates Dual Mechanisms in Pancreatic Ductal Adenocarcinoma: Stemness Association and PI3K/Akt-Mediated Progression
Provisionally accepted- 1First Affiliated Hospital of Harbin Medical University, Harbin, China
- 2Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai, Guangdong Province, China
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Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with limited treatment options, where cancer stem cells (CSCs) contribute to therapy resistance and poor prognosis. Identifying novel stemness-related biomarkers is crucial for improving PDAC management. Methods: Transcriptomic profiles of PDAC samples were acquired from public genomic repositories TCGA. The RNAss tumor stemness index was calculated from the samples' methylation and mRNA profiles. Hub genes were detected via weighted gene co-expression network analysis (WGCNA) combined with cross-validation of differential expression patterns. The immune microenvironment were analyzed via the ssGSEA algorithm. Quantification of PCDH1 expression in PDAC utilizing qRT-PCR, Western blotting, and immunohistochemistry assays. Evaluation of proliferation and migration capacities via assays of MTT, colony formation, Transwell migration, and wound healing. Characterization of cancer stem cell properties through flow cytometric sorting coupled with 3D spheroid culture systems. Results: PCDH1 was identified as a key stemness-related gene, significantly correlated with poor prognosis. Knockdown of PCDH1 suppressed proliferation, migration, and stemness markers (CD24/CD133) while impairing sphere formation. Mechanistically, PCDH1 activated the PI3K/Akt pathway, and its depletion reduced downstream signaling. PCDH1 expression also negatively correlated with immune infiltration, suggesting a role in immune evasion. Conclusion: Our findings establish PCDH1 as a critical regulator of PDAC stemness and progression, highlighting its potential as a therapeutic target to overcome CSCdriven resistance in PDAC.
Keywords: Pancreatic Ductal Adenocarcinoma, Stemness index, Pcdh1, proliferation, immune cell
Received: 13 Mar 2025; Accepted: 11 Apr 2025.
Copyright: © 2025 Yang, Zhipeng, Song, Dai, Zhang and Zhao. 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:
Weihui Zhang, First Affiliated Hospital of Harbin Medical University, Harbin, China
Dali Zhao, First Affiliated Hospital of Harbin Medical University, Harbin, China
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.