Young Aggressive Prostate Tumors Exhibit Increased Genomic Instability and an Exploratory RNA–CNA-Concordant Transcriptomic Pattern
4 affiliations
- 1Unidad Regional Mazatlán, Laboratorio de Investigación Biomédica y Biotecnológica, Universidad Autónoma de Occidente, Av. del Mar 1200, Col. Tellería, Mazatlán C.P. 82100, Sinaloa, Mexico
- 2Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Sinaloa, Ciudad Universitaria, Calz. de las Américas Nte. 2771, Col. Burócrata, Culiacán Rosales C.P. 80030, Sinaloa, Mexico
- 3Unidad de Investigaciones en Salud Pública “Dra. Kaethe Willms”, Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Sinaloa, Ciudad Universitaria, Culiacán Rosales C.P. 80013, Sinaloa, Mexico
- 4Unidad Regional Los Mochis, Departamento Académico de Ciencias de la Salud, Universidad Autónoma de Occidente, Blvd. Macario Gaxiola y Carretera Internacional México 15, Los Mochis C.P. 81223, Sinaloa, Mexico
Abstract
Prostate cancer (PCa) is a highly heterogeneous disease, and the molecular features underlying differences in tumor aggressiveness remain incompletely understood. This study aimed to characterize the molecular differences between young aggressive (YA) and old indolence-associated (OI) prostate tumors using an integrative multi-omics approach. RNA sequencing, copy number alteration (CNA), and clinical data from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) cohort were analyzed. YA tumors (age ≤ 58 years, Gleason score ≥ 8; n = 30) were compared with OI tumors (age ≥ 67 years, Gleason score ≤ 7; n = 41). YA tumors exhibited higher FGA and a greater nominal frequency of homozygous PTEN deletion, consistent with increased genomic instability. Transcriptomic analysis identified 1083 differentially expressed genes, whereas integrative RNA–CNA analysis prioritized 40 exploratory concordant genes, 35 of which showed copy-number loss-associated downregulation. Sensitivity analyses showed that 8 of 40 genes retained both the predefined FDR and effect-size criteria after tumor-purity adjustment, whereas only one gene retained both criteria after additional adjustment for pT and N. Functional enrichment and network analyses identified metabolic and homeostatic programs and a central interaction module within the original prioritized gene set. These findings provide exploratory hypotheses regarding molecular differences between the two predefined extreme phenotypes.
Related
- Pheochromocytomas with Aggressive Histopathological Features Have Reduced Apelin and Increased VEGF Expression: Diagnostic and Prognostic Implications.
- Integrative Bioinformatics and Exploratory Experimental Validation of Expression Changes in miR-214-3p, miR-1b, miR-133b-3p, and Directionally Concordant mRNAs in a Rat Model of Acute Myocardial Infarction
- Efficacy of tactile stimulation via vibratory ankle supports and insoles on proprioception and balance in functional ankle instability: an exploratory four-armed randomized trial
- Selection Instability and External Performance of Transcriptomic Models Beyond Age, Sex and Stage in Resected Lung Adenocarcinoma
- Identification of Five Candidate Genes and Development of an Exploratory Diagnostic Nomogram for COPD Using Integrative Single-Cell and Bulk Transcriptomic Analyses.
BibTeX
@article{bergezhernandez2026young,
title = {{Young Aggressive Prostate Tumors Exhibit Increased Genomic Instability and an Exploratory RNA–CNA-Concordant Transcriptomic Pattern}},
author = {Fernando Bergez-Hernández and Alejandra Martínez-Camberos and Geovanni Romero-Quintana and Jesús Parra-Unda and Lennin Garrido-Palazuelos and Martín Irigoyen Arredondo},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27188316},
url = {https://www.mdpi.com/1422-0067/27/18/8316},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Young Aggressive Prostate Tumors Exhibit Increased Genomic Instability and an Exploratory RNA–CNA-Concordant Transcriptomic Pattern
AU - Fernando Bergez-Hernández
AU - Alejandra Martínez-Camberos
AU - Geovanni Romero-Quintana
AU - Jesús Parra-Unda
AU - Lennin Garrido-Palazuelos
AU - Martín Irigoyen Arredondo
PY - 2026
DA - 2026/09/18
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27188316
UR - https://www.mdpi.com/1422-0067/27/18/8316
AB - Prostate cancer (PCa) is a highly heterogeneous disease, and the molecular features underlying differences in tumor aggressiveness remain incompletely understood. This study aimed to characterize the molecular differences between young aggressive (YA) and old indolence-associated (OI) prostate tumors using an integrative multi-omics approach. RNA sequencing, copy number alteration (CNA), and clinical data from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) cohort were analyzed. YA tumors (age ≤ 58 years, Gleason score ≥ 8; n = 30) were compared with OI tumors (age ≥ 67 years, Gleason score ≤ 7; n = 41). YA tumors exhibited higher FGA and a greater nominal frequency of homozygous PTEN deletion, consistent with increased genomic instability. Transcriptomic analysis identified 1083 differentially expressed genes, whereas integrative RNA–CNA analysis prioritized 40 exploratory concordant genes, 35 of which showed copy-number loss-associated downregulation. Sensitivity analyses showed that 8 of 40 genes retained both the predefined FDR and effect-size criteria after tumor-purity adjustment, whereas only one gene retained both criteria after additional adjustment for pT and N. Functional enrichment and network analyses identified metabolic and homeostatic programs and a central interaction module within the original prioritized gene set. These findings provide exploratory hypotheses regarding molecular differences between the two predefined extreme phenotypes.
SN - 1422-0067
ER -