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


RESULTS
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.


METHODS
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.


CONCLUSIONS
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.
Department of Otolaryngology and Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mariana
M
Brait
Department of Otolaryngology and Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mithu
M
Banerjee
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.
Leonel
L
Maldonado
Department of Otolaryngology and Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Akira
A
Ooki
Department of Otolaryngology and Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Myriam
M
Loyo
Department of Otolaryngology and Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Elisa
E
Guida
Department of Otolaryngology and Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Evgeny
E
Izumchenko
Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Leslie
L
Mangold
Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Elizabeth
E
Humphreys
Department of Urological Oncology, Davidoff Center, Beilinson Hospital, Eliahu Hakim, Ramat Aviv, Israel.
Eli
E
Rosenbaum
Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Alan
A
Partin
Department of Otolaryngology and Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
David
D
Sidransky
Department of Otolaryngology and Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.|Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Mohammad Obaidul
MO
Hoque
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D051929:CD146 Antigen / Q000097:blood / Q000235:genetics; D019175:DNA Methylation; D047628:Estrogen Receptor alpha / Q000097:blood / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood / Q000235:genetics; D019048:Prostatic Intraepithelial Neoplasia / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D012372:ROC Curve
D014408:Biomarkers, Tumor; D051929:CD146 Antigen; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C497902:MCAM protein, human; D017430:Prostate-Specific Antigen
early detection; methylation; prostate cancer