The clinical and biological significance of TBRG4 expression in prostate cancer
- 1Department of Urology, The Second Hospital & Clinical Medical School, Lanzhou University
- 2Gansu Province Clinical Research Center for Urinary System Diseases, Institute of Urology, The Second Hospital of Lanzhou University
- 3Lanzhou University Second Hospital
Abstract
Background: Transforming growth factor beta regulator 4 (TBRG4), regulates mitochondrial RNA processing. TBRG4 has been implicated in the progression of several malignancies, but its biological function and clinical relevance in prostate cancer remain unclear.
Methods: Publicly available data from The Cancer Genome Atlas prostate adenocarcinoma cohort and three Gene Expression Omnibus cohorts were analyzed. Differential expression was assessed independently in TCGA-PRAD, GSE88808, GSE46602, and GSE70768. Progression-free survival (PFS) was evaluated in TCGA-PRAD. External PFS analyses were conducted in GSE70768 and GSE46602 using the publicly available biochemical-recurrence status and corresponding follow-up time. Gain- and loss-of-function experiments were performed in PC3 and DU145 cells, which showed the highest baseline TBRG4 expression among the tested prostate cancer cell lines. A PC3 subcutaneous xenograft was used for in vivo validation.
Results: TBRG4 was upregulated in the analyzed PCa cohorts and cell lines and was associated with higher Gleason score, prostate-specific antigen level, and pathologic T category. High TBRG4 expression was associated with shorter PFS in TCGA-PRAD in univariable analysis [hazard ratio (HR), 2.138; 95% confidence interval (CI), 1.180–3.872; P = 0.012], but not after multivariable adjustment (HR, 1.411; 95% CI, 0.771–2.582; P = 0.264). TBRG4 overexpression increased colony formation, migration, invasion, and wound closure and was accompanied by decreased E-cadherin and increased N-cadherin and vimentin expression. TBRG4 knockdown produced the opposite effects. High TBRG4 expression was associated with phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin pathway enrichment, and TBRG4 manipulation was accompanied by changes in pathway-protein phosphorylation. TBRG4 knockdown also reduced PC3 xenograft growth.
Conclusions: TBRG4 is upregulated across the evaluated prostate cancer cohorts and is associated with adverse clinicopathological features in TCGA-PRAD. Functionally, TBRG4 supports tumor growth and invasive phenotypes, accompanied by changes in PI3K/AKT/mTOR signaling. Associations between TBRG4 expression and progression-free survival were observed in selected cohorts, suggesting that TBRG4 may represent a prognostic factor in prostate cancer.
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BibTeX
@article{li2026clinical,
title = {{The clinical and biological significance of TBRG4 expression in prostate cancer}},
author = {Wenxuan Li and Xi Xiao and Ting Wang and Yang Liu and Shuai Liu and Xin Guan and Rundong Li and Kun Zhao and Zhongze Zhou and Yang Bai and Yunchen Miao and Yan Tao and Zhilong Dong},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1982091},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1982091/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The clinical and biological significance of TBRG4 expression in prostate cancer
AU - Wenxuan Li
AU - Xi Xiao
AU - Ting Wang
AU - Yang Liu
AU - Shuai Liu
AU - Xin Guan
AU - Rundong Li
AU - Kun Zhao
AU - Zhongze Zhou
AU - Yang Bai
AU - Yunchen Miao
AU - Yan Tao
AU - Zhilong Dong
PY - 2026
DA - 2026/10/29
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1982091
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1982091/full
AB - Background: Transforming growth factor beta regulator 4 (TBRG4), regulates mitochondrial RNA processing. TBRG4 has been implicated in the progression of several malignancies, but its biological function and clinical relevance in prostate cancer remain unclear. Methods: Publicly available data from The Cancer Genome Atlas prostate adenocarcinoma cohort and three Gene Expression Omnibus cohorts were analyzed. Differential expression was assessed independently in TCGA-PRAD, GSE88808, GSE46602, and GSE70768. Progression-free survival (PFS) was evaluated in TCGA-PRAD. External PFS analyses were conducted in GSE70768 and GSE46602 using the publicly available biochemical-recurrence status and corresponding follow-up time. Gain- and loss-of-function experiments were performed in PC3 and DU145 cells, which showed the highest baseline TBRG4 expression among the tested prostate cancer cell lines. A PC3 subcutaneous xenograft was used for in vivo validation. Results: TBRG4 was upregulated in the analyzed PCa cohorts and cell lines and was associated with higher Gleason score, prostate-specific antigen level, and pathologic T category. High TBRG4 expression was associated with shorter PFS in TCGA-PRAD in univariable analysis [hazard ratio (HR), 2.138; 95% confidence interval (CI), 1.180–3.872; P = 0.012], but not after multivariable adjustment (HR, 1.411; 95% CI, 0.771–2.582; P = 0.264). TBRG4 overexpression increased colony formation, migration, invasion, and wound closure and was accompanied by decreased E-cadherin and increased N-cadherin and vimentin expression. TBRG4 knockdown produced the opposite effects. High TBRG4 expression was associated with phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin pathway enrichment, and TBRG4 manipulation was accompanied by changes in pathway-protein phosphorylation. TBRG4 knockdown also reduced PC3 xenograft growth. Conclusions: TBRG4 is upregulated across the evaluated prostate cancer cohorts and is associated with adverse clinicopathological features in TCGA-PRAD. Functionally, TBRG4 supports tumor growth and invasive phenotypes, accompanied by changes in PI3K/AKT/mTOR signaling. Associations between TBRG4 expression and progression-free survival were observed in selected cohorts, suggesting that TBRG4 may represent a prognostic factor in prostate cancer.
SN - 2234-943X
ER -