Centre de recherche du Centre hospitalier de l'Université de Montréal et Institut du cancer de Montréal, Montreal, Canada.
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United Kingdom.
Cancer Epidemiol Biomarkers Prev. 2022 Apr 1;31(4):715-727. doi: 10.1158/1055-9965.EPI-21-0600.
The need to better understand the molecular underpinnings of the heterogeneous outcomes of patients with prostate cancer is a pressing global problem and a key research priority for Movember. To address this, the Movember Global Action Plan 1 Unique tissue microarray (GAP1-UTMA) project constructed a set of unique and richly annotated tissue microarrays (TMA) from prostate cancer samples obtained from multiple institutions across several global locations.
Three separate TMA sets were built that differ by purpose and disease state.
The intended use of TMA1 (Primary Matched LN) is to validate biomarkers that help determine which clinically localized prostate cancers with associated lymph node metastasis have a high risk of progression to lethal castration-resistant metastatic disease, and to compare molecular properties of high-risk index lesions within the prostate to regional lymph node metastases resected at the time of prostatectomy. TMA2 (Pre vs. Post ADT) was designed to address questions regarding risk of castration-resistant prostate cancer (CRPC) and response to suppression of the androgen receptor/androgen axis, and characterization of the castration-resistant phenotype. TMA3 (CRPC Met Heterogeneity)'s intended use is to assess the heterogeneity of molecular markers across different anatomic sites in lethal prostate cancer metastases.
The GAP1-UTMA project has succeeded in combining a large set of tissue specimens from 501 patients with prostate cancer with rich clinical annotation.
This resource is now available to the prostate cancer community as a tool for biomarker validation to address important unanswered clinical questions around disease progression and response to treatment.
更好地了解前列腺癌患者结果存在异质性的分子基础,是一个紧迫的全球性问题,也是莫特龙(Movember)的一个关键研究重点。为此,莫特龙全球行动计划 1 号独特组织微阵列(GAP1-UTMA)项目从多个全球地点的多个机构获得的前列腺癌样本中构建了一组独特且内容丰富的组织微阵列(TMA)。
构建了三个不同目的和疾病状态的 TMA 集。
TMA1(原发匹配淋巴结)的预期用途是验证有助于确定哪些具有相关淋巴结转移的临床局限性前列腺癌具有进展为致命去势抵抗转移性疾病的高风险的生物标志物,并比较前列腺内高风险指数病变与前列腺切除术时切除的区域淋巴结转移的分子特性。TMA2(去势治疗前 vs. 后)旨在解决关于去势抵抗性前列腺癌(CRPC)风险和对雄激素受体/雄激素轴抑制的反应以及对去势抵抗表型的特征描述的问题。TMA3(CRPC 转移的异质性)的预期用途是评估致命性前列腺癌转移中不同解剖部位的分子标志物的异质性。
GAP1-UTMA 项目成功地将 501 名前列腺癌患者的大量组织标本与丰富的临床注释相结合。
该资源现在可供前列腺癌社区用作验证生物标志物的工具,以解决有关疾病进展和对治疗反应的重要未解答的临床问题。