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

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

Research output: Contribution to journalArticle

11 Citations (Scopus)

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, ERa 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, ERa, 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, ERa 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.

Original languageEnglish (US)
Pages (from-to)15431-15440
Number of pages10
JournalOncotarget
Volume8
Issue number9
DOIs
StatePublished - 2017
Externally publishedYes

Fingerprint

Methylation
Prostatic Neoplasms
Prostate-Specific Antigen
Serum
Sensitivity and Specificity
Prostate
Biomarkers
Prostatic Intraepithelial Neoplasia
Biopsy
Early Detection of Cancer
Epigenomics
Neoplasms
Polymerase Chain Reaction
Genes

Keywords

  • Early detection
  • Methylation
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Brait, M., Banerjee, M., Maldonado, L., Ooki, A., Loyo, M., Guida, E., ... Hoque, M. O. (2017). Promoter methylation of MCAM, ERa and ERβ in serum of early stage prostate cancer patients. Oncotarget, 8(9), 15431-15440. https://doi.org/10.18632/oncotarget.14873

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

In: Oncotarget, Vol. 8, No. 9, 2017, p. 15431-15440.

Research output: Contribution to journalArticle

Brait, M, Banerjee, M, Maldonado, L, Ooki, A, Loyo, M, Guida, E, Izumchenko, E, Mangold, L, Humphreys, E, Rosenbaum, E, Partin, A, Sidransky, D & Hoque, MO 2017, 'Promoter methylation of MCAM, ERa and ERβ in serum of early stage prostate cancer patients', Oncotarget, vol. 8, no. 9, pp. 15431-15440. https://doi.org/10.18632/oncotarget.14873
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. / Promoter methylation of MCAM, ERa and ERβ in serum of early stage prostate cancer patients. In: Oncotarget. 2017 ; Vol. 8, No. 9. pp. 15431-15440.
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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, ERa 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, ERa, 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, ERa 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.",
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T1 - Promoter methylation of MCAM, ERa and ERβ in serum of early stage prostate cancer patients

AU - Brait, Mariana

AU - Banerjee, Mithu

AU - Maldonado, Leonel

AU - Ooki, Akira

AU - Loyo, Myriam

AU - Guida, Elisa

AU - Izumchenko, Evgeny

AU - Mangold, Leslie

AU - Humphreys, Elizabeth

AU - Rosenbaum, Eli

AU - Partin, Alan

AU - Sidransky, David

AU - Hoque, Mohammad Obaidul

PY - 2017

Y1 - 2017

N2 - 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, ERa 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, ERa, 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, ERa 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.

AB - 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, ERa 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, ERa, 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, ERa 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.

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KW - Methylation

KW - Prostate cancer

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