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ORIGINAL RESEARCH ARTICLE

Dual roles of FGF2 and PGR in lactate-driven metabolic reprogramming and immune evasion: Implications for prostate cancer outcomes

Bo Peng1† ,  Rongbo Xue2† ,  Xuhua Qiao2 ,  Chundong Ji2*
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1 Department of Urology, Jianyang People’s Hospital, Chengdu, Sichuan, China
2 Department of Urology, Affiliated Hospital of Panzhihua University, Panzhihua Hospital of Integrated Traditional Chinese and Western Medicine, Clinical and Basic Research Team of Urinary System Diseases, Affiliated Hospital of Panzhihua University, Research and Innovation Platform of Panzhihua Urology, Panzhihua, Sichuan, China
†These authors contributed equally to this work.
EJMO, 025230251 https://doi.org/10.36922/EJMO025230251
Received: 8 June 2025 | Revised: 15 October 2025 | Accepted: 10 November 2025 | Published online: 16 December 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Prostate cancer (PCa) continues to present significant therapeutic challenges, particularly in advanced stages. Lactate, a pivotal metabolite within the tumor microenvironment, promotes tumor progression through mechanisms involving metabolic reprogramming and immune suppression. Fibroblast growth factor 2 (FGF2) and progesterone receptor (PGR) represent lactate metabolism-associated genes implicated in PCa pathogenesis; however, their immunomodulatory functions and prognostic relevance remain incompletely characterized.

Methods: Multi-omics data derived from public repositories (e.g., TCGA-PRAD, GEO, ImmPort) were systematically integrated to screen out genes related to lactate metabolism and immune cell infiltration. Analyses encompassed functional enrichment, immune infiltration profiling (QuanTIseq), and single-cell transcriptomics. Cox regression, coupled with least absolute shrinkage and selection operator regularization, identified FGF2 and PGR as hub genes. A clinical–molecular prognostic signature was subsequently developed and rigorously validated employing receiver operating characteristic curves, decision curve analysis, and calibration plots.

Results: FGF2 and PGR demonstrated enrichment in biological processes, including angiogenesis and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway signaling, alongside associations with immunosuppressive cell infiltration (e.g., tumor-associated macrophages [TAM] and regulatory T cells). Single-cell resolution analysis revealed predominant expression within fibroblast and macrophage populations. Although elevated co-expression levels correlated with a prolonged progression-free interval, they concurrently corresponded to increased drug resistance, as indicated by higher half-maximal inhibitory concentration values. A combined prognostic model incorporating these genes and established clinical factors demonstrated robust predictive accuracy (area under the curve = 0.85).

Conclusion: FGF2 and PGR modulate lactate-mediated immune–metabolic crosstalk within the PCa tumor microenvironment, influencing TAM polarization and regulatory T-cell activity, thereby exerting context-dependent pro- and anti-tumorigenic effects. These findings highlight that FGF2 and PGR are promising therapeutic targets for combination strategies, although further mechanistic elucidation and clinical validation are warranted.

Keywords
Lactate metabolism
Immune microenvironment
Prostate cancer prognosis
Fibroblast growth factor 2
Progesterone receptor
Funding
This study was supported by the Science and Technology Bureau of Panzhihua City (2021zx-5-2) and the Panzhihua Medical Research Center (PYYZ-2022-02) and the Health Commission of Sichuan Province Medical Science and Technology Program(24WSXT005).
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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