Promoter methylation of MCAM, ERα and ERβ in serum of early stage prostate cancer patients.

Mariana Brait,Leonel Maldonado,Akira Ooki,Elisa Guida,Myriam Loyo,Evgeny Izumchenko,David Sidransky,Elizabeth Humphreys,Mohammad Obaidul Hoque,Eli Rosenbaum,Leslie Mangold,Mithu Banerjee,Alan Partin

doi:10.18632/oncotarget.14873

Abstract

BackgroundProstate 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.ResultsThe 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.Materials and MethodsSixteen 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.ConclusionsPromoter 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.

Highlights

Prostate cancer (PC) is the most frequent cancer among men in the United States and 180,890 men are estimated to be diagnosed with PC in the USA in 2016, with 26,120 estimated deaths due to this cancer type [1]
The sensitivity and specificity of hypermethylation of MCAM was 66% and 73% respectively which is an improvement from the sensitivity and specificity of prostate-specific antigen (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

Summary

Introduction

Prostate cancer (PC) is the most frequent cancer among men in the United States and 180,890 men are estimated to be diagnosed with PC in the USA in 2016, with 26,120 estimated deaths due to this cancer type [1]. The main tool for diagnosis of PC is Digital Rectal Examination (DRE) and the main tool for screening and risk assessment is serum prostate-specific antigen (sPSA). After the implementation of the sPSA test in the clinic, the detection of PC dramatically increased with a peak in the early 1990s. Early detection of PC substantially improved due to routine sPSA testing, there is no consensus regarding whether this test effectively reduces the risk of death from the disease [3]. The unsatisfactory correlation between sPSA levels and disease state leads to unnecessary biopsies [5]. The most common non-invasive approach for screening and risk assessment of PC is measuring the level of serum prostate-specific antigen (PSA).

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