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

Autor: Evgeny Izumchenko, David Sidransky, Eli Rosenbaum, Elisa Guida, Akira Ooki, Mohammad O. Hoque, Myriam Loyo, Leonel Maldonado, Leslie A. Mangold, Mariana Brait, Mithu Banerjee, Alan W. Partin, Elizabeth B. Humphreys
Rok vydání: 2017
Předmět:
Adult
Male
0301 basic medicine
Oncology
medicine.medical_specialty
Pathology
CD146 Antigen
Polymerase Chain Reaction
03 medical and health sciences
Prostate cancer
0302 clinical medicine
Prostate
Internal medicine
Biomarkers
Tumor
medicine
Estrogen Receptor beta
Humans
Prospective Studies
High-grade prostatic intraepithelial neoplasia
Promoter Regions
Genetic
early detection
Prospective cohort study
Aged
Neoplasm Staging
Prostatic Intraepithelial Neoplasia
business.industry
Estrogen Receptor alpha
Prostatic Neoplasms
Cancer
DNA Methylation
Middle Aged
Prostate-Specific Antigen
prostate cancer
medicine.disease
3. Good health
030104 developmental biology
medicine.anatomical_structure
ROC Curve
Otorhinolaryngology
030220 oncology & carcinogenesis
Cohort
Biomarker (medicine)
methylation
business
Research Paper
Zdroj: Oncotarget
ISSN: 1949-2553
DOI: 10.18632/oncotarget.14873
Popis: // Mariana Brait 1, * , Mithu Banerjee 1, * , Leonel Maldonado 1, 4 , Akira Ooki 1 , Myriam Loyo 1 , Elisa Guida 1 , Evgeny Izumchenko 1 , Leslie Mangold 2 , Elizabeth Humphreys 2 , Eli Rosenbaum 5 , Alan Partin 2 , David Sidransky 1, 3 , Mohammad Obaidul Hoque 1, 2, 3 1 Department of Otolaryngology and Head and Neck Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 2 Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 3 Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA 4 Department of Pathology, University of South Alabama Medical Center, Mobile, Alabama, USA 5 Department of Urological Oncology, Davidoff Center, Beilinson Hospital, Eliahu Hakim, Ramat Aviv, Israel * These authors contributed equally to this work Correspondence to: Mohammad Obaidul Hoque, email: mhoque1@jhmi.edu Keywords: prostate cancer, methylation, early detection Received: June 08, 2016 Accepted: December 31, 2016 Published: January 28, 2017 ABSTRACT 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. Materials and 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.
Databáze: OpenAIRE
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