Harvard/Michigan Prostate Cancer Biomarker Clinical Ctr

描述（由申请人提供）：尽管其广泛使用，但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改善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中的合作努力，本文聚集的研究者已经基于癌性而非正常前列腺组织中α-甲基酰基-CoA消旋酶（AMACR）表达的生物学后果确定了前列腺癌早期检测的途径。初步数据表明，循环抗AMACR自身抗体在前列腺癌患者外周血中的检出率高于对照患者。此外，我们观察到具有侵袭性病理特征的癌症患者血清中的抗AMACR自身抗体滴度高于具有更惰性前列腺癌的患者。为了建立在这些初步数据的基础上，我们组建了一个多学科，多机构的研究人员团队，在4个机构（Beth Israel-Deaconess Medical Center，Brigham and Women's Hospital，Dana Farber Cancer Institute和密歇根大学）建立了一个中心，用于对此类AMACR靶向以及其他候选新型前列腺癌生物标志物进行临床验证。该提案的主要假设是，对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措施的原型）与前列腺癌的存在和严重程度显著相关，并且为改善前列腺癌的早期检测提供了机会。将通过评价从三个补充临床队列中采集的血清来解决这一假设。这些队列中的每一个都提供了评价三个目标的互补优势和局限性，这些目标共同解决了以下研究假设： 1.在接受前列腺活检的男性前瞻性病例对照队列中，比较抗AMACR抗体存在的特异性与PSA检测前列腺癌的特异性。为此目的，将入组1800例活检病例。 2.在医生健康研究队列（一个基于社区的前列腺癌和非前列腺癌医生队列）中，验证体液应答对组织生物标志物（包括AMACR）检测癌症和衡量癌症严重程度的准确性。为此目的，将对500例前列腺癌病例和1500例对照进行评价。 3.在接受前列腺癌治疗的男性队列中，评价抗AMACR抗体或针对前列腺组织生物标志物的其他体液应答的存在是否可以区分侵袭性前列腺癌与前列腺外扩散风险较低的早期癌症。为此目的，将对1500例前列腺癌病例进行评价。 我们将从3个目的组合的总计4700例受试者中收集外周血和相关临床信息，并将这些标本扩展到EDRN的其他合作生物标志物研究。

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.