Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target

Clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and therapeutic target

Prostate cancer (PCa) is the second most common cancer among men worldwide. The main screening tool remains the prostate-specific antigen (PSA), which shows significant limitations, including poor sensitivity/specificity. Therefore, establishing accurate non-invasive diagnostic biomarkers remains an...

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Main Authors: Antonio J. Montero-Hidalgo, Enrique Gómez-Gómez, Manuel Galán-Cañete, Francisco Porcel-Pastrana, Jesús M. Pérez-Gómez, María Ortega-Bellido, Julia Carrasco-Valiente, Laura Chamorro-Castillo, Juan P. Campos-Hernández, Oriol A. Rangel-Zuñiga, Teresa González-Serrano, Rafael Sánchez-Sánchez, André Sarmento-Cabral, Manuel D. Gahete, Juan M. Jiménez-Vacas, Raúl M. Luque
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Molecular Therapy: Oncology
Subjects:
MT: Novel therapeutic targets and biomarker development Special Issue
SRRM1
SNRNP200
SRSF3
prostate cancer
biomarker
Online Access:http://www.sciencedirect.com/science/article/pii/S2950329924001528
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Summary:Prostate cancer (PCa) is the second most common cancer among men worldwide. The main screening tool remains the prostate-specific antigen (PSA), which shows significant limitations, including poor sensitivity/specificity. Therefore, establishing accurate non-invasive diagnostic biomarkers remains an unmet clinical need in PCa. In this context, the splicing process dysregulation represents a PCa hallmark. Here, plasma SRRM1, SNRNP200, and SRSF3 levels, previously identified to play a pathophysiological role in PCa, were determined in control individuals (n = 40) and PCa patients (n = 166). We found that plasma SRRM1 and SNRNP200 levels were elevated in PCa patients and discriminated between control individuals and PCa patients. High plasma SRRM1 levels were associated with a shorter castration-resistant PCa-free survival and correlated with androgen-receptor (AR)/AR-splicing variant 7 (AR-V7) expression levels and activity in PCa tissues. Therefore, the functional and molecular effects of in vivo SRRM1 silencing were then tested in 22Rv1-derived xenograft tumors. In vivo SRRM1 silencing reduced aggressiveness features and altered AR/AR-V7 activity. Our data reveal that SRRM1 holds potential as a non-invasive diagnostic and prognostic biomarker and novel therapeutic target in PCa, offering a clinically relevant opportunity worth exploring in humans.
ISSN:2950-3299

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