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ORIGINAL RESEARCH ARTICLE

Exploring the therapeutic potential of gamma-glutamyl carboxylase in prostate cancer through integrated multi-omics analysis

Yuangao Xu1† ,  Jieyu Xiong2† ,  Yuanbo Xu3 ,  YiKun Wu4 ,  Yuanlin Wang5 ,  Hua Shi5* ,  Shuxiong Xu5*
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1 Department of Organ Transplantation, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, China
2 Department of Biomedical Research, Faculty of Medicine, University of Bern, Bern, Switzerland
3 Department of Clinical Medicine, School of Medicine, Southern Medical University, Guangzhou, Guangdong, China
4 Department of Clinical Medicine, School of Medicine, Guizhou University, Guiyang, Guizhou, China
5 Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, China
†These authors contributed equally to this work.
EJMO, 025320342 https://doi.org/10.36922/EJMO025320342
Received: 4 August 2025 | Revised: 1 December 2025 | Accepted: 10 December 2025 | Published online: 22 January 2026
© 2026 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) treatment is often limited by heterogeneous therapeutic responses and the emergence of drug resistance, underscoring the urgent need to identify novel therapeutic targets.

Objective: This study aims to identify novel susceptibility genes associated with PCa risk by integrating genomic, transcriptomic, and proteomic data.

Methods: We performed a genome-wide summary-data-based Mendelian randomization (SMR) analysis leveraging cis-expression quantitative trait loci from multiple tissues and PCa phenotypes. We then applied Bayesian colocalization to confirm that the observed SMR signals reflected shared causal variants. To characterize gamma-glutamyl carboxylase (GGCX) expression in normal and malignant prostate tissues, we integrated bulk transcriptomic and proteomic data from The Cancer Genome Atlas, Gene Expression Omnibus, the International Cancer Genome Consortium, and the Human Protein Atlas. We further investigated the spatial distribution of GGCX within the tumor microenvironment using spatial transcriptomics and Spearman correlation analyses with key stromal and immune cell markers. Finally, we constructed a GGCX-centered gene set by combining weighted gene co-expression network analysis with a random forest model and performed GO and KEGG enrichment analyses to infer its potential biological functions and pathways.

Results: SMR identified 53 candidate genes associated with PCa phenotypes, including GGCX (p<0.001), and confirmed the association of GGCX using Bayesian colocalization (PP.H4 > 0.95). GGCX expression was higher in PCa tissues than in normal prostate tissues (p<0.001), and it was positively correlated with tumor cell abundance but inversely correlated with fibroblast content in PCa. We further found that a GGCX-associated gene set was enriched in the ubiquinone and terpenoid-quinone biosynthesis pathway, particularly the vitamin K cycle.

Conclusion: Our multi-omics data highlight the GGCX–vitamin K axis as a genetically supported and druggable pathway in PCa.

Keywords
Susceptibility gene
Gamma-glutamyl carboxylase
Prostate cancer
Multi-omics study
Funding
This study was funded by the National Natural Science Foundation of China under grant numbers 82160145 and 82460154, as well as the 2021 National Natural Science Foundation Post Subsidy Individual Fund of China, reference GPPH-NSFC-2021-10. Furthermore, it received support from the Science and Technology Fund of the Guizhou Health Commission, grant number gzwkj2021-212.
Conflict of interest
The authors declare that they have no competing interests.
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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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