ORIGINAL RESEARCH article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1589259
This article is part of the Research TopicThe Role of Cell Metabolism in Development, Drug Resistance, and Survival Assessment in CancerView all 5 articles
Impact of ITH on PRAD patients and feasibility analysis of the positive correlation gene MYLK2 applied to PRAD treatment
Provisionally accepted
- 1Department of Andrology and Sexual Medicine, The Second Hospital of Dalian Medical University, Dalian, China
- 2Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, China
- 3Department of hepatobiliary surgery, Dalian Friendship Hospital, dalian, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
AbstractIntroduction: Prostate adenocarcinoma (PRAD) is the second most common male cancer worldwide. Immunotherapy progress is slow due to its "cold tumour" nature and high intra-tumour heterogeneity (ITH). This study investigates the potential of using ITH levels to guide clinical treatment.Methods: PRAD clinical and transcriptomic data from TCGA were analysed. ITH-scores were calculated using the DEPTH algorithm, dividing patients into high- and low-ITH groups. Differentially expressed genes (DEGs) associated with ITH were identified, and a prognostic signature was developed through Cox regression. Functional enrichment, immune infiltration analyses, drug prediction, and model validation were performed. MYLK2 was selected as a key gene and validated through cellular experiments.Results: Lower ITH-scores correlated with better survival. Four key genes (SYNPO2L, MYLK2, CKM, MYL3) were identified. Pathway analysis showed enrichment in muscle contraction. Significant differences in immune landscapes and immunotherapy responsiveness were observed between high- and low-ITH groups. NU.1025 was identified as a potential therapeutic drug. The random survival forest model showed strong predictive performance. MYLK2 was confirmed to promote PRAD cell proliferation and migration.Discussion: ITH is a promising biomarker for PRAD prognosis. MYLK2 could serve as a novel therapeutic target, offering new treatment strategies for PRAD patients.
Keywords: prostate adenocarcinoma (PRAD), intra-tumour heterogeneity (ITH), prognosis, Immunotherapy, MYLK2
Received: 11 Mar 2025; Accepted: 05 May 2025.
Copyright: © 2025 Ma, Li, Song, Qi and Jiang. 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:
Xiaochen Qi, Department of Urology, First Affiliated Hospital of Dalian Medical University, Dalian, China
Tao Jiang, Department of Andrology and Sexual Medicine, The Second Hospital of Dalian Medical University, Dalian, 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.