Harvard/Michigan Prostate Cancer Biomarker Clinical Ctr

描述（由申请人提供）：尽管广泛使用，血清前列腺特异性抗原（PSA）作为前列腺癌生物标志物的准确性有限，需要新的生物标志物来提高侵袭性前列腺癌的早期检测。通过在前列腺癌生物标志物开发方面的合作努力，在此聚集的研究人员已经确定了基于癌变而非正常前列腺组织中α -甲基酰基辅酶a消旋酶（AMACR）表达的生物学后果的前列腺癌早期检测途径。初步数据表明，前列腺癌患者外周血中循环抗amacr自身抗体的检出率高于对照组患者。此外，我们观察到具有侵袭性病理特征的前列腺癌患者的血清中抗amacr自身抗体滴度高于较惰性前列腺癌患者。在这些初步数据的基础上，我们组建了一个多学科、多机构的研究团队，在4个机构（Beth israeli - deaconess医疗中心、Brigham and Women’s医院、Dana Farber癌症研究所和密歇根大学）建立了一个以amacr为靶点以及其他候选新型前列腺癌生物标志物的临床验证中心。本提案的主要假设是，AMACR的体液免疫应答（作为与前列腺癌相关的AMACR表达相关的各种临床测量的原型）与前列腺癌的存在和严重程度显著相关，并为改善前列腺癌的早期检测提供了机会。这一假设将通过评估从三个互补的临床队列收集的血清来解决。每个队列在评估三个目标时提供了互补的优势和局限性，这些目标共同解决了以下研究假设：

DESCRIPTION (provided by applicant): Despite its widespread use, serum Prostate-Specific Antigen (PSA) has limited accuracy as a prostate cancer biomarker, and new biomarkers are needed to improve early detection of aggressive prostate cancers. Through a collaborative effort in prostate cancer biomarker development, investigators assembled herein have identified avenues for prostate cancer early detection based on biological consequences of alpha-methylacyl-CoA racemase (AMACR) expression in cancerous, but not normal, prostate tissue. Preliminary data indicate that circulating anti-AMACR autoantibodies are detectable in the peripheral blood of prostate cancer patients at higher rates than among control patients. Moreover, we observed higher anti-AMACR auto-antibody titers in sera of patients that had cancers with aggressive pathological features than among patients with more indolent prostate cancer. To build upon these preliminary data, we have assembled a multi-disciplinary, multi-institutional team of investigators to establish a center for the clinical validation of such AMACR-targeted as well as other candidate novel prostate cancer biomarkers at 4 institutions (Beth Israel-Deaconess Medical Center, Brigham and Women's Hospital, Dana Farber Cancer Institute, and the University of Michigan). The primary hypothesis of this proposal is that a humoral immune response to AMACR (as a prototype of various clinical measures related to prostate cancer-associated AMACR expression) is significantly associated with presence and severity of prostate cancer, and provides an opportunity for improvements in early detection of prostate cancer. This hypothesis will be addressed through evaluation of serum collected from three complementary clinical cohorts. Each of these cohorts provides complementary strengths and limitations in evaluating three aims that together address the study hypothesis as follows: 1. To compare specificity of anti-AMACR antibody presence to the specificity of PSA for detecting prostate cancer in a prospective case-control cohort of men undergoing prostate biopsy. 1800 biopsy cases will be enrolled for this Aim. 2. To validate the accuracy of humoral responses against tissue biomarkers, including AMACR, in detecting cancers and gauging cancer severity in the Physicians' Health Study cohort, a community-based cohort of physicians with and without prostate cancer. 500 prostate cancer cases and 1500 controls will be evaluated for this Aim. 3. To evaluate whether anti-AMACR antibody or presence of other humoral responses against prostatic tissue biomarkers) can distinguish aggressive prostate cancers from early cancers at lower risk for extra-prostatic spread in a cohort of men treated for prostate cancer. 1500 prostate caner cases will be evaluated for this Aim. We will collect peripheral blood and relevant clinical information from an aggregate total of 4700 subjects between the 3 Aims combined, and will extend these specimens for other, collaborative biomarker studies of the EDRN.