PTEN Deletion, mTORC1 Signatures and CAD Expression in Primary Prostate Cancer: Protein-Level Data and the Role of ERG Fusion
7 affiliations
- 1College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
- 2Department of Biotechnology, Utkal University, Vani Vihar, Bhubaneswar 751004, Odisha, India
- 3Department of Health Informatics, College of Applied Medical Sciences, Qassim University, Buraydah 51452, Saudi Arabia
- 4College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia
- 5King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard–Health Affairs, Riyadh 11481, Saudi Arabia
- 6Department of Biotechnology, School of Life Sciences, Central University of Kashmir, Ganderbal 191201, Jammu and Kashmir, India
- 7Research Center, King Faisal Specialist Hospital and Research Center, Jeddah 21499, Saudi Arabia
Abstract
PTEN loss activates PI3K–AKT signaling, and mTORC1 stimulates pyrimidine synthesis through S6K1-mediated CAD phosphorylation. This exploratory public-data analysis tested whether PTEN deletion in primary prostate cancer is associated with CAD, mTORC1 and pyrimidine-synthesis expression, and whether these survive protein-level and confounder analyses. In 485 primary tumors from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD; 159 PTEN-deleted), deletion was associated with higher CAD mRNA (Hedges’ g = 0.57) and higher Hallmark mTORC1 scores (g = 0.54). In 342 tumors with reverse-phase protein-array data, deletion was accompanied by lower PTEN protein and higher AKT Ser473 phosphorylation but not by a higher pre-specified mTORC1 phospho-output composite (g = −0.02), itself uncorrelated with the transcriptional score. In a pre-specified model adding purity, TP53, RB1, ERG fusion and batch (n = 276), the PTEN–CAD association was absent (β = −0.002; p = 0.96), whereas the mTORC1-score association persisted. In a post hoc decomposition, ERG fusion, which co-occurs with PTEN deletion (odds ratio 3.6), changed the coefficient most. Across eight cohorts, a small PTEN mRNA–CAD association (g = 0.23) was attenuated to 0.14 after ERG adjustment, with overlapping confidence intervals (Hartung–Knapp p = 0.071). Bulk-tumor pathway signatures and PTEN–CAD associations need protein-level and ERG-aware interpretation.
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BibTeX
@article{arora2026pten,
title = {{PTEN Deletion, mTORC1 Signatures and CAD Expression in Primary Prostate Cancer: Protein-Level Data and the Role of ERG Fusion}},
author = {Itika Arora and Suvasmita Rath and Qazi Mohammad Sajid Jamal and Ahmed Aljohani and Abid Hamid and Ahmed Abu-Zaid and Mohammad Imran Khan and Ahmed Yaqinuddin},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211997},
url = {https://www.mdpi.com/2073-4409/15/21/1997},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - PTEN Deletion, mTORC1 Signatures and CAD Expression in Primary Prostate Cancer: Protein-Level Data and the Role of ERG Fusion
AU - Itika Arora
AU - Suvasmita Rath
AU - Qazi Mohammad Sajid Jamal
AU - Ahmed Aljohani
AU - Abid Hamid
AU - Ahmed Abu-Zaid
AU - Mohammad Imran Khan
AU - Ahmed Yaqinuddin
PY - 2026
DA - 2026/10/31
JO - Cells
DO - 10.3390/cells15211997
UR - https://www.mdpi.com/2073-4409/15/21/1997
AB - PTEN loss activates PI3K–AKT signaling, and mTORC1 stimulates pyrimidine synthesis through S6K1-mediated CAD phosphorylation. This exploratory public-data analysis tested whether PTEN deletion in primary prostate cancer is associated with CAD, mTORC1 and pyrimidine-synthesis expression, and whether these survive protein-level and confounder analyses. In 485 primary tumors from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD; 159 PTEN-deleted), deletion was associated with higher CAD mRNA (Hedges’ g = 0.57) and higher Hallmark mTORC1 scores (g = 0.54). In 342 tumors with reverse-phase protein-array data, deletion was accompanied by lower PTEN protein and higher AKT Ser473 phosphorylation but not by a higher pre-specified mTORC1 phospho-output composite (g = −0.02), itself uncorrelated with the transcriptional score. In a pre-specified model adding purity, TP53, RB1, ERG fusion and batch (n = 276), the PTEN–CAD association was absent (β = −0.002; p = 0.96), whereas the mTORC1-score association persisted. In a post hoc decomposition, ERG fusion, which co-occurs with PTEN deletion (odds ratio 3.6), changed the coefficient most. Across eight cohorts, a small PTEN mRNA–CAD association (g = 0.23) was attenuated to 0.14 after ERG adjustment, with overlapping confidence intervals (Hartung–Knapp p = 0.071). Bulk-tumor pathway signatures and PTEN–CAD associations need protein-level and ERG-aware interpretation.
SN - 2073-4409
ER -