PO.MCB10.01 · 分子与细胞生物学

外泌体microRNA作为西班牙裔转移性去势抵抗性前列腺癌男性疾病进展的表观遗传生物标志物

Exosomal micrornas as epigenetic biomarkers of disease progression in Hispanic men with metastatic castration-resistant prostate cancer

编号 2048 展板 8 时间 4/20 09:00–12:00 区域 Section 25 主讲 Carmen Ortiz-Sanchez, PhD

分会场 MicroRNAs as Cancer Biomarkers, Therapeutic Targets, and Modulators of Treatment Response

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作者与单位 Authors & Affiliations

Carmen M. Ortiz-Sanchez¹, Jarline Encarnacion¹, Stephanie Montalvo², Shakira Abad³, Gabriela Castro³, Lenin Godoy¹, Ralphdy Vergne¹, Jong Y. Park⁴, Gilberto Ruiz-Deya¹

¹Ponce Health Sciences University, Ponce, Puerto Rico,²University of Puerto Rico at Mayaguez, Mayaguez, Puerto Rico,³Pontificia Universidad Católica de Puerto Rico, Ponce, Puerto Rico,⁴Moffitt Cancer Center, Tampa, FL

摘要 Abstract

中文摘要

背景：转移性去势抵抗性前列腺癌（mCRPC）是局限性前列腺肿瘤对雄激素剥夺治疗（ADT）不再有反应并发展出转移潜能时出现的。尽管治疗手段不断进步，mCRPC仍无法治愈，中位生存期仅9-13个月。因此，识别能够帮助早期检测和监测疾病进展的表观遗传生物标志物（如外泌体microRNA，exo-miRNA）至关重要，尤其是在西班牙裔男性等代表性不足的人群中。方法：分析了波多黎各前列腺癌男性在局限期和转移期的配对血浆样本（n=11），以识别与进展至mCRPC相关的exo-miRNA。从血浆中分离外泌体，提取总exo-miRNA，并在Moffitt癌症中心使用nCounter Human v3 miRNA Expression Assay（NanoString Technologies）进行表达谱分析。数据经过归一化处理，统计显著性采用双样本t检验和Welch's t检验进行评估。所有分析均在R（v4.5.1）中使用tidyverse、readr和ggplot2程序包完成。结果：在排除对照和加标后，初始表达矩阵（M）包含798个miRNA。同质性评估得到一个精炼后的66个靶标矩阵。应用SD=1阈值识别出18个在疾病进展过程中差异表达的候选miRNA。其中，miR-302d-3p（p=0.01）和miR-23a-3p（p=0.045）在局限性与转移性疾病之间发生显著改变。另外六个候选（miR-1246、miR-16-5p、miR-199a-3p/miR-199b-3p、miR-2053）显示出临界显著性（p<0.05），提示潜在的生物学相关性。本研究为西班牙裔男性前列腺癌进展的表观遗传格局提供了新的见解，突出了循环exo-miRNA作为疾病监测的微创生物标志物。鉴于来自该人群的临床标本有限，这些发现尤为重要。循环exo-miRNA特征的识别提供了一种监测疾病进展的微创方法，并最终有望支持开发用于晚期前列腺癌早期检测和风险分层的血液生物标志物。资助：由American Cancer Society Institutional Research Grant（ACS-IRG Subaward No. 60-21510-99-20）、来自Puerto Rico Science, Technology & Research Trust（PRST）的Catalyzer Research Grant，以及Ponce Health Sciences University与Moffitt癌症中心之间的NIH/NCI U54 Partnership Grants（U54CA163071和U54CA163068）资助。

查看英文原文 English abstract

Background: Metastatic castration-resistant prostate cancer (mCRPC) arises when localized prostate tumors become unresponsive to androgen deprivation therapy (ADT) and develop metastatic potential. Despite therapeutic advances, mCRPC remains incurable, with a median survival of only 9-13 months. Identifying epigenetic biomarkers, such as exosomal microRNAs (exo-miRNAs), that can aid in early detection and monitoring disease progression is therefore critical, particularly among underrepresented populations such as Hispanic men. Methods: Matched plasma samples from Puerto Rican men with prostate cancer at localized and metastatic stages (n=11) were analyzed to identify exo-miRNAs associated with progression to mCRPC. Exosomes were isolated from plasma, total exo-miRNAs were extracted, and expression profiling was performed using the nCounter Human v3 miRNA Expression Assay (NanoString Technologies) at Moffitt Cancer Center. Data were normalized, and statistical significance was evaluated using two-sample t-test and the Welch's t-test. All analyses were performed in R (v4.5.1) using the tidyverse, readr, and ggplot2 packages. Results: The initial expression matrix (M) contained 798 miRNAs after excluding controls and spike-ins. Homogeneity assessment yielded a refined matrix of 66 targets. Applying an SD=1 threshold identified 18 candidate miRNAs differentially expressed during disease progression. Among these, miR-302d-3p (p=0.01) and miR-23a-3p (p=0.045) were significantly altered between localized and metastatic disease. Six additional candidates (miR-1246, miR-16-5p, miR-199a-3p/miR-199b-3p, miR-2053) showed borderline significance (p<0.05), suggesting potential biological relevance. This study provides novel insight into the epigenetic landscape of prostate cancer progression among Hispanic men, highlighting circulating exo-miRNAs as minimally invasive biomarkers for disease monitoring. Given the limited availability of clinical specimens from this population, these findings are particularly significant. The identification of circulating exo-miRNA signatures offers a minimally invasive approach to monitor disease progression and could ultimately support the development of blood-based biomarkers for early detection and risk stratification in advanced prostate cancer. Funding: Supported by the American Cancer Society Institutional Research Grant (ACS-IRG Subaward No. 60-21510-99-20), the Catalyzer Research Grant from the Puerto Rico Science, Technology & Research Trust (PRST), and the NIH/NCI U54 Partnership Grants (U54CA163071 & U54CA163068) between Ponce Health Sciences University and Moffitt Cancer Center.

利益披露 Disclosure

C. M. Ortiz-Sanchez, None.. J. Encarnacion, None.. S. Montalvo, None.. S. Abad, None.. G. Castro, None.. L. Godoy, None.. R. Vergne, None.. G. Ruiz-Deya, None.

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