Brait Mariana, Banerjee Mithu, Maldonado Leonel, Ooki Akira, Loyo Myriam, Guida Elisa, Izumchenko Evgeny, Mangold Leslie, Humphreys Elizabeth, Rosenbaum Eli, Partin Alan, Sidransky David, Hoque Mohammad Obaidul
Department of Otolaryngology and Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Department of Pathology, University of South Alabama Medical Center, Mobile, Alabama, USA.
Oncotarget. 2017 Feb 28;8(9):15431-15440. doi: 10.18632/oncotarget.14873.
Prostate cancer (PC) is the second most common cancer among men worldwide. Currently, the most common non-invasive approach for screening and risk assessment of PC is measuring the level of serum prostate-specific antigen (PSA). However, the sensitivity of PSA is 42.8 % and specificity is 41.1%. As a result, the serum PSA test leads to numerous unneeded biopsies. Therefore, a rigorous search for biomarkers for early detection of PC is ongoing. In this study, we aim to assess a panel of epigenetic markers in an intend to develop an early detection test for PC.
The sensitivity and specificity of hypermethylation of MCAM was 66% and 73% respectively which is an improvement from the sensitivity and specificity of PSA. Considering a combination marker panel of MCAM, ERα and ERβ increased the sensitivity to 75% and the specificity became 70% for the minimally invasive early detection test of PC.
Sixteen primary matched tumor and serum were analyzed by quantitative methylation specific PCR (QMSP) to determine analytical and clinical sensitivity of the genes tested (SSBP2, MCAM, ERα, ERβ, APC, CCND2, MGMT, GSTP1, p16 and RARβ2). Additionally, serum samples from eighty four cases of PC, thirty controls and seven cases diagnosed as high grade Prostatic Intraepithelial Neoplasia (HGPIN) were analyzed.
Promoter methylation of MCAM, ERα and ERβ have a potential to be utilized as biomarker for the early detection of prostate PC as their sensitivity and specificity seem to be better than serum PSA in our cohort of samples. After robust validation in a larger prospective cohort, our findings may reduce the numbers of unwarranted prostate biopsies.
前列腺癌（PC）是全球男性中第二常见的癌症。目前，用于前列腺癌筛查和风险评估的最常见非侵入性方法是测量血清前列腺特异性抗原（PSA）水平。然而，PSA的敏感性为42.8%，特异性为41.1%。因此，血清PSA检测导致大量不必要的活检。因此，目前正在进行严格的前列腺癌早期检测生物标志物的研究。在本研究中，我们旨在评估一组表观遗传标志物，以期开发一种前列腺癌早期检测测试。
MCAM高甲基化的敏感性和特异性分别为66%和73%，这比PSA的敏感性和特异性有所提高。考虑到MCAM、ERα和ERβ的联合标志物组，前列腺癌微创早期检测测试的敏感性提高到75%，特异性变为70%。
通过定量甲基化特异性PCR（QMSP）分析16对原发性匹配肿瘤和血清，以确定所检测基因（SSBP2、MCAM、ERα、ERβ、APC、CCND2、MGMT、GSTP1、p16和RARβ2）的分析敏感性和临床敏感性。此外，还分析了84例前列腺癌患者、30例对照和7例诊断为高级别前列腺上皮内瘤变（HGPIN）患者的血清样本。
MCAM、ERα和ERβ的启动子甲基化有潜力用作前列腺癌早期检测的生物标志物，因为在我们的样本队列中，它们的敏感性和特异性似乎优于血清PSA。在更大的前瞻性队列中进行有力验证后，我们的发现可能会减少不必要的前列腺活检数量。
