Skip to main content
Top
Published in: Tumor Biology 4/2014

01-04-2014 | Research Article

The association between RASSF1A promoter methylation and prostate cancer: evidence from 19 published studies

Authors: Yu-Zheng Ge, Lu-Wei Xu, Rui-Peng Jia, Zheng Xu, Yu-Ming Feng, Ran Wu, Peng Yu, Yan Zhao, Zan-Long Gui, Si-Jia Tan, Qun Song

Published in: Tumor Biology | Issue 4/2014

Login to get access

Abstract

Ras-associated domain family 1A (RASSF1A) is a putative tumor suppressor gene located at 3p21.3, and the epigenetic inactivation of RASSF1A by hypermethylation of CpG islands within the promoter region has been observed in various cancer types, including prostate cancer (PCa). However, results from published studies on the association between RASSF1A promoter methylation and PCa risk are conflicting and inconclusive. Hence, we conducted a meta-analysis of 19 eligible studies with odds ratio (OR) and its corresponding 95% confidence intervals (95% CI) in order to investigate the strength of relationship of RASSF1A promoter methylation with PCa risk and its clinicopathological variables. Overall, the RASSF1A promoter methylation was significantly associated with PCa risk (OR = 9.58, 95% CI 5.64–16.88, P heterogeneity <0.001) and Gleason score (GS) (OR = 2.58, 95% CI 1.64–4.04, P heterogeneity = 0.019). In addition, subgroup analysis by testing material demonstrated the significant association between RASSF1A methylation and GS (OR = 3.09, 95% CI 1.92–4.97, P heterogeneity =0.042), PSA level (OR = 2.75, 95% CI 1.67–4.52, P heterogeneity = 0.639), and tumor stage (OR = 1.74, 95% CI 1.05–2.87, P heterogeneity = 0.026) in tissue rather than urine samples. In conclusion, this meta-analysis suggested that RASSF1A promoter methylation was significantly associated with an increased risk for PCa; furthermore, the RASSF1A methylation status in tissue rather than urine was positively correlated with GS, serum PSA level, and tumor stage, which can be utilized for the early detection and prognosis prediction of PCa.
Literature
11.
go back to reference Dammann R, Li C, Yoon JH, Chin PL, Bates S, Pfeifer GP. Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet. 2000;25(3):315–9. doi:10.1038/77083.PubMedCrossRef Dammann R, Li C, Yoon JH, Chin PL, Bates S, Pfeifer GP. Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet. 2000;25(3):315–9. doi:10.​1038/​77083.PubMedCrossRef
12.
go back to reference Maruyama R, Toyooka S, Toyooka KO, Virmani AK, Zochbauer-Muller S, Farinas AJ, et al. Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features. Clin Cancer Res. 2002;8(2):514–9.PubMed Maruyama R, Toyooka S, Toyooka KO, Virmani AK, Zochbauer-Muller S, Farinas AJ, et al. Aberrant promoter methylation profile of prostate cancers and its relationship to clinicopathological features. Clin Cancer Res. 2002;8(2):514–9.PubMed
15.
go back to reference Singal R, Ferdinand L, Reis IM, Schlesselman JJ. Methylation of multiple genes in prostate cancer and the relationship with clinicopathological features of disease. Oncol Rep. 2004;12(3):631–7.PubMed Singal R, Ferdinand L, Reis IM, Schlesselman JJ. Methylation of multiple genes in prostate cancer and the relationship with clinicopathological features of disease. Oncol Rep. 2004;12(3):631–7.PubMed
18.
go back to reference Bastian PJ, Ellinger J, Wellmann A, Wernert N, Heukamp LC, Muller SC, et al. Diagnostic and prognostic information in prostate cancer with the help of a small set of hypermethylated gene loci. Clin Cancer Res. 2005;11(11):4097–106. doi:10.1158/1078-0432.CCR-04-1832.PubMedCrossRef Bastian PJ, Ellinger J, Wellmann A, Wernert N, Heukamp LC, Muller SC, et al. Diagnostic and prognostic information in prostate cancer with the help of a small set of hypermethylated gene loci. Clin Cancer Res. 2005;11(11):4097–106. doi:10.​1158/​1078-0432.​CCR-04-1832.PubMedCrossRef
19.
go back to reference Hoque MO, Topaloglu O, Begum S, Henrique R, Rosenbaum E, Van Criekinge W, et al. Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects. J Clin Oncol. 2005;23(27):6569–75. doi:10.1200/JCO.2005.07.009.PubMedCrossRef Hoque MO, Topaloglu O, Begum S, Henrique R, Rosenbaum E, Van Criekinge W, et al. Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects. J Clin Oncol. 2005;23(27):6569–75. doi:10.​1200/​JCO.​2005.​07.​009.PubMedCrossRef
20.
go back to reference Cho NY, Kim BH, Choi M, Yoo EJ, Moon KC, Cho YM, et al. Hypermethylation of CpG island loci and hypomethylation of LINE-1 and Alu repeats in prostate adenocarcinoma and their relationship to clinicopathological features. J Pathol. 2007;211(3):269–77. doi:10.1002/path.2106.PubMedCrossRef Cho NY, Kim BH, Choi M, Yoo EJ, Moon KC, Cho YM, et al. Hypermethylation of CpG island loci and hypomethylation of LINE-1 and Alu repeats in prostate adenocarcinoma and their relationship to clinicopathological features. J Pathol. 2007;211(3):269–77. doi:10.​1002/​path.​2106.PubMedCrossRef
21.
go back to reference Roupret M, Hupertan V, Yates DR, Catto JW, Rehman I, Meuth M, et al. Molecular detection of localized prostate cancer using quantitative methylation-specific PCR on urinary cells obtained following prostate massage. Clin Cancer Res. 2007;13(6):1720–5. doi:10.1158/1078-0432.CCR-06-2467.PubMedCrossRef Roupret M, Hupertan V, Yates DR, Catto JW, Rehman I, Meuth M, et al. Molecular detection of localized prostate cancer using quantitative methylation-specific PCR on urinary cells obtained following prostate massage. Clin Cancer Res. 2007;13(6):1720–5. doi:10.​1158/​1078-0432.​CCR-06-2467.PubMedCrossRef
23.
go back to reference Henrique R, Ribeiro FR, Fonseca D, Hoque MO, Carvalho AL, Costa VL, et al. High promoter methylation levels of APC predict poor prognosis in sextant biopsies from prostate cancer patients. Clin Cancer Res. 2007;13(20):6122–9. doi:10.1158/1078-0432.CCR-07-1042.PubMedCrossRef Henrique R, Ribeiro FR, Fonseca D, Hoque MO, Carvalho AL, Costa VL, et al. High promoter methylation levels of APC predict poor prognosis in sextant biopsies from prostate cancer patients. Clin Cancer Res. 2007;13(20):6122–9. doi:10.​1158/​1078-0432.​CCR-07-1042.PubMedCrossRef
24.
go back to reference Roupret M, Hupertan V, Catto JW, Yates DR, Rehman I, Proctor LM, et al. Promoter hypermethylation in circulating blood cells identifies prostate cancer progression. Int J Cancer. 2008;122(4):952–6. doi:10.1002/ijc.23196.PubMedCrossRef Roupret M, Hupertan V, Catto JW, Yates DR, Rehman I, Proctor LM, et al. Promoter hypermethylation in circulating blood cells identifies prostate cancer progression. Int J Cancer. 2008;122(4):952–6. doi:10.​1002/​ijc.​23196.PubMedCrossRef
25.
go back to reference Syeed N, Syed Sameer A, Hamid A, Shah ZA, Afroze D, Rasool R, et al. Promoter methylation profile of GSTP1 and RASSF1A in benign hyperplasia and metastatic prostate cancer patients in a Kashmiri population. Mol Med Rep. 2010;3(5):883–7. doi:10.3892/mmr.2010.348.PubMed Syeed N, Syed Sameer A, Hamid A, Shah ZA, Afroze D, Rasool R, et al. Promoter methylation profile of GSTP1 and RASSF1A in benign hyperplasia and metastatic prostate cancer patients in a Kashmiri population. Mol Med Rep. 2010;3(5):883–7. doi:10.​3892/​mmr.​2010.​348.PubMed
26.
go back to reference Liu L, Kron KJ, Pethe VV, Demetrashvili N, Nesbitt ME, Trachtenberg J, et al. Association of tissue promoter methylation levels of APC, TGFbeta2, HOXD3 and RASSF1A with prostate cancer progression. Int J Cancer. 2011;129(10):2454–62. doi:10.1002/ijc.25908.PubMedCrossRef Liu L, Kron KJ, Pethe VV, Demetrashvili N, Nesbitt ME, Trachtenberg J, et al. Association of tissue promoter methylation levels of APC, TGFbeta2, HOXD3 and RASSF1A with prostate cancer progression. Int J Cancer. 2011;129(10):2454–62. doi:10.​1002/​ijc.​25908.PubMedCrossRef
27.
go back to reference Vasiljevic N, Wu K, Brentnall AR, Kim DC, Thorat MA, Kudahetti SC, et al. Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing. Dis Markers. 2011;30(4):151–61. doi:10.3233/DMA-2011-0790.PubMedCrossRef Vasiljevic N, Wu K, Brentnall AR, Kim DC, Thorat MA, Kudahetti SC, et al. Absolute quantitation of DNA methylation of 28 candidate genes in prostate cancer using pyrosequencing. Dis Markers. 2011;30(4):151–61. doi:10.​3233/​DMA-2011-0790.PubMedCrossRef
28.
go back to reference Dimitriadis E, Kalogeropoulos T, Velaeti S, Sotiriou S, Vassiliou E, Fasoulis L, et al. Study of genetic and epigenetic alterations in urine samples as diagnostic markers for prostate cancer. Anticancer Res. 2013;33(1):191–7.PubMed Dimitriadis E, Kalogeropoulos T, Velaeti S, Sotiriou S, Vassiliou E, Fasoulis L, et al. Study of genetic and epigenetic alterations in urine samples as diagnostic markers for prostate cancer. Anticancer Res. 2013;33(1):191–7.PubMed
29.
30.
go back to reference Divyya S, Naushad SM, Murthy PV, Reddy CR, Kutala VK. GCPII modulates oxidative stress and prostate cancer susceptibility through changes in methylation of RASSF1, BNIP3, GSTP1 and Ec-SOD. Mol Biol Rep. 2013. doi:10.1007/s11033-013-2655-7. Divyya S, Naushad SM, Murthy PV, Reddy CR, Kutala VK. GCPII modulates oxidative stress and prostate cancer susceptibility through changes in methylation of RASSF1, BNIP3, GSTP1 and Ec-SOD. Mol Biol Rep. 2013. doi:10.​1007/​s11033-013-2655-7.
31.
go back to reference Yegnasubramanian S, Kowalski J, Gonzalgo ML, Zahurak M, Piantadosi S, Walsh PC, et al. Hypermethylation of CpG islands in primary and metastatic human prostate cancer. Cancer Res. 2004;64(6):1975–86.PubMedCrossRef Yegnasubramanian S, Kowalski J, Gonzalgo ML, Zahurak M, Piantadosi S, Walsh PC, et al. Hypermethylation of CpG islands in primary and metastatic human prostate cancer. Cancer Res. 2004;64(6):1975–86.PubMedCrossRef
32.
go back to reference Prior C, Guillen-Grima F, Robles JE, Rosell D, Fernandez-Montero JM, Agirre X, et al. Use of a combination of biomarkers in serum and urine to improve detection of prostate cancer. World J Urol. 2010;28(6):681–6. doi:10.1007/s00345-010-0583-x.PubMedCrossRef Prior C, Guillen-Grima F, Robles JE, Rosell D, Fernandez-Montero JM, Agirre X, et al. Use of a combination of biomarkers in serum and urine to improve detection of prostate cancer. World J Urol. 2010;28(6):681–6. doi:10.​1007/​s00345-010-0583-x.PubMedCrossRef
33.
go back to reference Padar A, Sathyanarayana UG, Suzuki M, Maruyama R, Hsieh JT, Frenkel EP, et al. Inactivation of cyclin D2 gene in prostate cancers by aberrant promoter methylation. Clin Cancer Res. 2003;9(13):4730–4.PubMed Padar A, Sathyanarayana UG, Suzuki M, Maruyama R, Hsieh JT, Frenkel EP, et al. Inactivation of cyclin D2 gene in prostate cancers by aberrant promoter methylation. Clin Cancer Res. 2003;9(13):4730–4.PubMed
34.
go back to reference Kang GH, Lee S, Lee HJ, Hwang KS. Aberrant CpG island hypermethylation of multiple genes in prostate cancer and prostatic intraepithelial neoplasia. J Pathol. 2004;202(2):233–40. doi:10.1002/path.1503.PubMedCrossRef Kang GH, Lee S, Lee HJ, Hwang KS. Aberrant CpG island hypermethylation of multiple genes in prostate cancer and prostatic intraepithelial neoplasia. J Pathol. 2004;202(2):233–40. doi:10.​1002/​path.​1503.PubMedCrossRef
35.
go back to reference Woodson K, Gillespie J, Hanson J, Emmert-Buck M, Phillips JM, Linehan WM, et al. Heterogeneous gene methylation patterns among pre-invasive and cancerous lesions of the prostate: a histopathologic study of whole mount prostate specimens. Prostate. 2004;60(1):25–31. doi:10.1002/pros.20013.PubMedCrossRef Woodson K, Gillespie J, Hanson J, Emmert-Buck M, Phillips JM, Linehan WM, et al. Heterogeneous gene methylation patterns among pre-invasive and cancerous lesions of the prostate: a histopathologic study of whole mount prostate specimens. Prostate. 2004;60(1):25–31. doi:10.​1002/​pros.​20013.PubMedCrossRef
39.
go back to reference Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719–48.PubMed Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719–48.PubMed
40.
42.
go back to reference Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.PubMedCrossRef Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics. 1994;50(4):1088–101.PubMedCrossRef
44.
go back to reference Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.PubMedCentralPubMedCrossRef Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535.PubMedCentralPubMedCrossRef
45.
go back to reference Dammann R, Schagdarsurengin U, Strunnikova M, Rastetter M, Seidel C, Liu L, et al. Epigenetic inactivation of the Ras-association domain family 1 (RASSF1A) gene and its function in human carcinogenesis. Histol Histopathol. 2003;18(2):665–77.PubMed Dammann R, Schagdarsurengin U, Strunnikova M, Rastetter M, Seidel C, Liu L, et al. Epigenetic inactivation of the Ras-association domain family 1 (RASSF1A) gene and its function in human carcinogenesis. Histol Histopathol. 2003;18(2):665–77.PubMed
46.
go back to reference Pfeifer GP, Dammann R. Methylation of the tumor suppressor gene RASSF1A in human tumors. Biochemistry (Mosc). 2005;70(5):576–83.PubMedCrossRef Pfeifer GP, Dammann R. Methylation of the tumor suppressor gene RASSF1A in human tumors. Biochemistry (Mosc). 2005;70(5):576–83.PubMedCrossRef
47.
go back to reference Kuzmin I, Gillespie JW, Protopopov A, Geil L, Dreijerink K, Yang Y, et al. The RASSF1A tumor suppressor gene is inactivated in prostate tumors and suppresses growth of prostate carcinoma cells. Cancer Res. 2002;62(12):3498–502.PubMed Kuzmin I, Gillespie JW, Protopopov A, Geil L, Dreijerink K, Yang Y, et al. The RASSF1A tumor suppressor gene is inactivated in prostate tumors and suppresses growth of prostate carcinoma cells. Cancer Res. 2002;62(12):3498–502.PubMed
Metadata
Title
The association between RASSF1A promoter methylation and prostate cancer: evidence from 19 published studies
Authors
Yu-Zheng Ge
Lu-Wei Xu
Rui-Peng Jia
Zheng Xu
Yu-Ming Feng
Ran Wu
Peng Yu
Yan Zhao
Zan-Long Gui
Si-Jia Tan
Qun Song
Publication date
01-04-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1515-3

Other articles of this Issue 4/2014

Tumor Biology 4/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine