ECEESPE2025 Rapid Communications Rapid Communications 9: Endocrine Related Cancer (5 abstracts)
Defining the clinical value of circulating splicing factors in prostate cancer: SRRM1 as a novel predictive biomarker and exploitable therapeutic target
Antonio Prats-Escribano 1 , Antonio Jesús Montero-Hidalgo 2 , Enrique Gómez-Gómez 3 , Manuel Galán-Cañete 2 , Ignacio Gil-Duque 2 , Francisco Porcel-Pastrana 2 , Jesús Miguel Pérez-Gómez 2 , María Ortega-Bellido 2 , Teresa González-Serrano 3 , Rafael Sánchez-Sánchez 3 , André Sarmento-Cabral 2 , Manuel David Gahete-Ortiz 2 , Juan Manuel Jiménez-Vacas 2 & Raúl Miguel Luque-Huertas 2
1Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain, Department of Cell Biology, Physiology, and Immunology, Córdoba, Spain; 2Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain, Hospital Universitario Reina Sofía (HURS), Cordoba, Spain, Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Cordoba, Spain, Córdoba, Spain; 3Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Cordoba, Spain, Hospital Universitario Reina Sofía (HURS), Cordoba, Spain, Córdoba, Spain
JOINT74
Prostate cancer (PCa) is the second most prevalent endocrine-related cancer among men worldwide. The main screening method, based on prostate-specific antigen (PSA) determination, exhibits significant limitations, including poor specificity and restricted prognostic value. Thus, the identification of accurate non-invasive diagnostic biomarkers, with potential prognostic and therapeutic applications, remains a critical need in PCa. In this context, dysregulation of the splicing process has emerged as a hallmark in PCa development and progression, with several splicing factors (SFs) playing key roles in PCa pathophysiology. However, despite discrete SFs have been reported to be potentially secreted by cancer cells, this event has not been addressed in PCa. Therefore, we aimed to explore the presence and potential clinical value of SRRM1, SNRNP200, and SRSF3 (previously reported SFs with a key pathophysiological role in PCa) in human plasma samples. Thus, plasma levels of these SFs were measured (using ELISAs) in control individuals (n=40) and PCa patients (n=166). We identified, for the first time, that these SFs were detectable in human plasma samples, being corroborated in an independent cohort of healthy individuals (n=313). Notably, plasma levels of SRRM1 and SNRNP200, but not SRSF3, were significantly elevated in PCa patients compared to controls. Furthermore, plasma and tissue SRRM1 levels were associated with relevant features of castration-resistant PCa (CRPC), a lethal disease stage, and positively correlated with androgen-receptor (AR) and AR-splicing variant 7 (AR-V7) expression and activity in PCa tissues. Furthermore, in vivo SRRM1 silencing in CRPC-derived xenografted tumors reduced aggressiveness features and AR/AR-V7 activity. Taken together, our findings suggest that circulating SRRM1 levels could serve as a valuable non-invasive diagnostic and prognostic biomarker in PCa. Additionally, SRRM1 may hold a promising therapeutic value, offering a clinically relevant opportunity for further exploration in human studies. Also, this study set the groundwork to thoroughly evaluate the presence and clinical utility of circulating SFs for clinical management of PCa patients.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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