Pecci Valeria, Pierconti Francesco, Carlino Angela, Pinto Francesco, Gradilone Ugo, De Martino Sara, Rotili Dante, Grassi Claudio, Pontecorvi Alfredo, Gaetano Carlo, Strigari Lidia, Farsetti Antonella, Nanni Simona
Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Fondazione "Policlinico Universitario A. Gemelli IRCCS", 00168 Rome, Italy.
Biomedicines. 2024 Oct 12;12(10):2322. doi: 10.3390/biomedicines12102322.
Metastatic prostate cancer (PCa) presents a significant challenge in oncology due to its high mortality rate and the absence of effective biomarkers for predicting patient outcomes. Building on previous research that highlighted the critical role of the long noncoding RNA (lncRNA) H19 and cell adhesion molecules in promoting tumor progression under hypoxia and estrogen stimulation, this study aimed to assess the potential of these components as prognostic biomarkers for PCa at the biopsy stage.
This research utilized immunohistochemistry and droplet digital PCR to analyze formalin-fixed paraffin-embedded (FFPE) biopsies, focusing on specific markers within the H19/cell adhesion molecules pathway.
A novel multivariate analysis led to a "BioScore", a composite biomarker score to predict disease progression. This score is based on evaluating five key markers: the expression levels of Hypoxia-Inducible Factor 2 Alpha (HIF-2α), endothelial Nitric Oxide Synthase (eNOS), β4 integrin, E-cadherin transcript (CDH1), and lncRNA H19. The criteria for the "BioScore" involve identifying three out of these five markers, combining elevated levels of HIF-2α, eNOS, β4 integrin, and CDH1 with reduced H19 expression.
This finding suggests the possibility of identifying, at the time of biopsy, PCa patients at higher risk of metastasis based on dysregulation in the H19/cell adhesion molecules circuitry. This study provides a valuable opportunity for early intervention in managing PCa, potentially contributing to personalized treatment strategies.
转移性前列腺癌（PCa）因其高死亡率以及缺乏预测患者预后的有效生物标志物，在肿瘤学领域构成了重大挑战。基于先前的研究突出了长链非编码RNA（lncRNA）H19和细胞粘附分子在缺氧和雌激素刺激下促进肿瘤进展中的关键作用，本研究旨在评估这些成分作为PCa活检阶段预后生物标志物的潜力。
本研究利用免疫组织化学和液滴数字PCR分析福尔马林固定石蜡包埋（FFPE）活检样本，重点关注H19/细胞粘附分子途径中的特定标志物。
一项新的多变量分析得出了一个“生物评分”，这是一种用于预测疾病进展的复合生物标志物评分。该评分基于对五个关键标志物的评估：缺氧诱导因子2α（HIF-2α）、内皮型一氧化氮合酶（eNOS）、β4整合素、E-钙粘蛋白转录本（CDH1）和lncRNA H19的表达水平。“生物评分”的标准包括从这五个标志物中识别出三个，将HIF-2α、eNOS、β4整合素和CDH1的高水平与H19表达降低相结合。
这一发现表明，在活检时，基于H19/细胞粘附分子通路失调识别出转移风险较高的PCa患者具有可能性。本研究为PCa的管理提供了早期干预的宝贵机会，可能有助于制定个性化治疗策略。
