Association between catechol-O-methyltransferase expression and the prognosis of prostate cancer
The enzyme catechol-O-methyltransferase (COMT) inhibits the proliferation of prostate cancer (PCa). We aimed to assess the possibility of using COMT expression as a biomarker for PCa progression in clinical specimens. We retrospectively evaluated tissue samples of 60 patients with PCa collected via...
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| Published in | Journal of Iwate Medical Assiociation Vol. 76; no. 2; pp. 35 - 44 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Iwate Medical Association
01.06.2024
岩手医学会 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0021-3284 2434-0855 |
| DOI | 10.24750/iwateishi.76.2_35 |
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| Abstract | The enzyme catechol-O-methyltransferase (COMT) inhibits the proliferation of prostate cancer (PCa). We aimed to assess the possibility of using COMT expression as a biomarker for PCa progression in clinical specimens. We retrospectively evaluated tissue samples of 60 patients with PCa collected via needle biopsy orradical prostatectomy. Immunostaining of COMT was performed using formalin-fixed, paraffin-embedded blocks obtained from the initial prostate biopsy for diagnosis or prostatectomy. Immunostaining evaluations were scored by immunostaining intensity ( 0 – 3 ) and staining area ( 0 – 3 ). A total score ≧ 4 was defined as “ high expression ” and a total score ＜ 4 was defined as “ low expression. ” The associations between COMT expression levels and clinical outcomes were assessed. Of the 60 cases, nine ( 15 %) showed low expression of COMT. Overall survival was significantly shorter in patients with lower COMT expression than those with higher COMT expression (hazard ratio [HR] = 0.24, 95 % confidence interval [CI] 0 . 07 – 0 . 83 , p = 0 . 024 ). Patients with lower COMT expression have a significantly poorer prognosis for PCa. To our knowledge, this is the first report of an association between COMT expression and the prognosis of prostate cancer in clinical specimens. |
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| AbstractList | The enzyme catechol-O-methyltransferase (COMT) inhibits the proliferation of prostate cancer (PCa). We aimed to assess the possibility of using COMT expression as a biomarker for PCa progression in clinical specimens. We retrospectively evaluated tissue samples of 60 patients with PCa collected via needle biopsy orradical prostatectomy. Immunostaining of COMT was performed using formalin-fixed, paraffin-embedded blocks obtained from the initial prostate biopsy for diagnosis or prostatectomy. Immunostaining evaluations were scored by immunostaining intensity ( 0 – 3 ) and staining area ( 0 – 3 ). A total score ≧ 4 was defined as “ high expression ” and a total score ＜ 4 was defined as “ low expression. ” The associations between COMT expression levels and clinical outcomes were assessed. Of the 60 cases, nine ( 15 %) showed low expression of COMT. Overall survival was significantly shorter in patients with lower COMT expression than those with higher COMT expression (hazard ratio [HR] = 0.24, 95 % confidence interval [CI] 0 . 07 – 0 . 83 , p = 0 . 024 ). Patients with lower COMT expression have a significantly poorer prognosis for PCa. To our knowledge, this is the first report of an association between COMT expression and the prognosis of prostate cancer in clinical specimens. The enzyme catechol-O-methyltransferase (COMT) inhibits the proliferation of prostate cancer (PCa). We aimed to assess the possibility of using COMT expression as a biomarker for PCa progression in clinical specimens. We retrospectively evaluated tissue samples of 60 patients with PCa collected via needle biopsy or radical prostatectomy. Immunostaining of COMT was performed using formalin-fixed, paraffin-embedded blocks obtained from the initial prostate biopsy for diagnosis or prostatectomy. Immunostaining evaluations were scored by immunostaining intensity ( 0 – 3 ) and staining area ( 0 – 3 ). A total score ≧ 4 was defined as “ high expression ” and a total score ＜ 4 was defined as “ low expression. ” The associations between COMT expression levels and clinical outcomes were assessed. Of the 60 cases, nine ( 15 %) showed low expression of COMT. Overall survival was significantly shorter in patients with lower COMT expression than those with higher COMT expression (hazard ratio [HR] = 0.24, 95 % confidence interval [CI] 0 . 07 – 0 . 83 , p = 0 . 024 ). Patients with lower COMT expression have a significantly poorer prognosis for PCa. To our knowledge, this is the first report of an association between COMT expression and the prognosis of prostate cancer in clinical specimens. |
| Author | 兼平 貢 菅井 有 杉本 亮 五十嵐 大樹 石川 健太 加藤 廉平 小原 航 前川 滋克 高田 亮 松浦 朋彦 |
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| References | Yang F, Song L, Wang H, et al.: Combination of quercetin and 2-Methoxyestradiol enhances inhibition of human prostate cancer LNCaP and PC-3 cells xenograft tumor growth. PLoS One 10, https://doi.org/10.1371/journal.pone.0128277, 2015. Hirata H, Hinoda Y, Okayama N, et al.: COMT polymorphisms affecting protein expression are risk factors for endometrial cancer. Mol Carcinog 47, 768-774, 2008. Grasso SC, Wu YM, Robinson RD, et al.: The mutational landscape of lethal castration-resistant prostate cancer. Nature 487, 239-243, 2012. Thibodeau PA and Paquette B: DNA damage induced by catecholestrogens in the presence of copper (II): generation of reactive oxygen species and enhancement by NADH. Free Radic Biol Med 27, 1367-1377, 1999. Tammimäki A, Kaënmäki M, Kambur O, et al.: Effect of S-COMT deficiency on behavior and extracellular brain dopamine concentrations in mice. Psychopharmacology 211, 389-401, 2010. Cavalieri EL, Stack DE, Devanesan PD, et al.: Molecular origin of cancer: catechol estrogen-3,4-quinones as endogenous tumor initiators. Proc Nati Acad Sci USA 94, 10937-10942, 1997. Ellingson T, Duddempudi S, Greenberg DB, et al.: Determination of differential activities of soluble and membrane-bound catechol-O-methyltransferase in tissues and erythrocytes. J Chromatogr B Biomed Sci Appl 729, 347-353, 1999. Hashimoto Y, Maekawa S, Shiina M, et al.: Suppressor effect of catechol-O-methyltransferase gene in prostate cancer. PLoS One 16, https://doi.org/10.1371/journal.pone.0253877, 2021. Thompson PA, Shields PG, Freudenheim JL, et al.: Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk. Cancer Res 58, 2107-2110, 1998. Batth IS, Huang SB, Villarreal M, et al.: Evidence for 2-Methoxyestradiol-mediated inhibition of receptor tyrosine kinase RON in the management of prostate cancer. Int J Mol Sci 22, https://doi.org/10.3390/ijms22041852, 2021. Xiao L, Tong M, Jin Y, et al.: The l58Val/Met polymorphism of catechol-O-methyl transferase gene and prostate cancer risk: a meta-analysis. Mol Biol Rep 40, 1835-1841, 2013. Huang CS, Chern HD, Chang KJ, et al.: Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility. Cancer Res 59, 4870-4875, 1999. Fabian MR, Sonenberg N and Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79, 351-379, 2010. Nelles LS, Hu WY and Prins SG: Estrogen action and prostate cancer. Expert Rev Endocrinol Metab 6, 437-451, 2011. Matos A, Castelao C, Alho I, et al.: Epistatic interaction of CYP1A1 and COMT polymorphisms in cervical cancer. Oxid Med Cell Longev 2016, https://doi.org/10.1155/2016/2769804, 2015. Sasaki M, Kaneuchi M, Sakuragi N, et al.: Multiple promoters of catechol-O-methyltransferase gene are selectively inactivated by CpG hypermethylation in endometrial cancer. Cancer Res 63, 3101-3106, 2003. Liehr JG: Dual role of estrogens as hormones and pro-carcinogens: tumour initiation by metabolic activation of estrogens. Eur J Cancer Prev 6, 3-10, 1997. Park SA, Na HK, Kim EH, et al.: 4-hydroxyestradiol induces anchorage-independent growth of human mammary epithelial cells via activation of IkappaB kinase: potential role of reactive oxygen species. Cancer Res 69, 2416-2424, 2009. Hashimoto M, Uesugi N, Sugai M, et al.: Desmoplastic reactions and epithelial-mesenchymal transition proteins in stages II and III colorectal cancer: association with and prognostic value for disease-free survival. Virchows Arch 480, 793-805, 2022. Mateo J, Seed G, Bertan C, et al.: Genomics of lethal prostate cancer at diagnosis and castration resistance. J Clin Invest 130, 1743-1751, 2020. Lajin B, Hamzeh AR, Ghabreau L, et al.: Catechol-O-methyltransferase Val108/158 Met polymorphism and breast cancer risk: a case control study in Syria. Breast Cancer 20, 62-66, 2013. Alhakamy NA, Ahmed OA, Fahmy UA, et al.: Development and in vitro evaluation of 2-Methoxyestradiol loaded polymeric micelles for enhancing anticancer activities in prostate cancer. Polymers (Basel) 13, https://doi.org/10.3390/polym13060884, 2021. Yager JD: Catechol-O-methyltransferase: characteristics, polymorphisms and role in breast cancer. Drug Discov Today Dis Mech 9, https://doi.org/10.1016/j.ddmec.2012.10.002, 2012. Sung H, Ferlay J, Siegel RL, et al.: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71, 209-249, 2021. Espinoza S, Manago F, Leo D, et al.: Role of catechol-O-methyltransferase (COMT)-dependent processes in Parkinson’s disease and L-DOPA treatment. CNS Neurol Disord Drug Targets 11, 251-263, 2012. |
| References_xml | – reference: Hashimoto M, Uesugi N, Sugai M, et al.: Desmoplastic reactions and epithelial-mesenchymal transition proteins in stages II and III colorectal cancer: association with and prognostic value for disease-free survival. Virchows Arch 480, 793-805, 2022. – reference: Huang CS, Chern HD, Chang KJ, et al.: Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility. Cancer Res 59, 4870-4875, 1999. – reference: Hirata H, Hinoda Y, Okayama N, et al.: COMT polymorphisms affecting protein expression are risk factors for endometrial cancer. Mol Carcinog 47, 768-774, 2008. – reference: Yang F, Song L, Wang H, et al.: Combination of quercetin and 2-Methoxyestradiol enhances inhibition of human prostate cancer LNCaP and PC-3 cells xenograft tumor growth. PLoS One 10, https://doi.org/10.1371/journal.pone.0128277, 2015. – reference: Ellingson T, Duddempudi S, Greenberg DB, et al.: Determination of differential activities of soluble and membrane-bound catechol-O-methyltransferase in tissues and erythrocytes. J Chromatogr B Biomed Sci Appl 729, 347-353, 1999. – reference: Matos A, Castelao C, Alho I, et al.: Epistatic interaction of CYP1A1 and COMT polymorphisms in cervical cancer. Oxid Med Cell Longev 2016, https://doi.org/10.1155/2016/2769804, 2015. – reference: Xiao L, Tong M, Jin Y, et al.: The l58Val/Met polymorphism of catechol-O-methyl transferase gene and prostate cancer risk: a meta-analysis. Mol Biol Rep 40, 1835-1841, 2013. – reference: Grasso SC, Wu YM, Robinson RD, et al.: The mutational landscape of lethal castration-resistant prostate cancer. Nature 487, 239-243, 2012. – reference: Tammimäki A, Kaënmäki M, Kambur O, et al.: Effect of S-COMT deficiency on behavior and extracellular brain dopamine concentrations in mice. Psychopharmacology 211, 389-401, 2010. – reference: Park SA, Na HK, Kim EH, et al.: 4-hydroxyestradiol induces anchorage-independent growth of human mammary epithelial cells via activation of IkappaB kinase: potential role of reactive oxygen species. Cancer Res 69, 2416-2424, 2009. – reference: Nelles LS, Hu WY and Prins SG: Estrogen action and prostate cancer. Expert Rev Endocrinol Metab 6, 437-451, 2011. – reference: Lajin B, Hamzeh AR, Ghabreau L, et al.: Catechol-O-methyltransferase Val108/158 Met polymorphism and breast cancer risk: a case control study in Syria. Breast Cancer 20, 62-66, 2013. – reference: Thibodeau PA and Paquette B: DNA damage induced by catecholestrogens in the presence of copper (II): generation of reactive oxygen species and enhancement by NADH. Free Radic Biol Med 27, 1367-1377, 1999. – reference: Sung H, Ferlay J, Siegel RL, et al.: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71, 209-249, 2021. – reference: Hashimoto Y, Maekawa S, Shiina M, et al.: Suppressor effect of catechol-O-methyltransferase gene in prostate cancer. PLoS One 16, https://doi.org/10.1371/journal.pone.0253877, 2021. – reference: Yager JD: Catechol-O-methyltransferase: characteristics, polymorphisms and role in breast cancer. Drug Discov Today Dis Mech 9, https://doi.org/10.1016/j.ddmec.2012.10.002, 2012. – reference: Espinoza S, Manago F, Leo D, et al.: Role of catechol-O-methyltransferase (COMT)-dependent processes in Parkinson’s disease and L-DOPA treatment. CNS Neurol Disord Drug Targets 11, 251-263, 2012. – reference: Mateo J, Seed G, Bertan C, et al.: Genomics of lethal prostate cancer at diagnosis and castration resistance. J Clin Invest 130, 1743-1751, 2020. – reference: Cavalieri EL, Stack DE, Devanesan PD, et al.: Molecular origin of cancer: catechol estrogen-3,4-quinones as endogenous tumor initiators. Proc Nati Acad Sci USA 94, 10937-10942, 1997. – reference: Batth IS, Huang SB, Villarreal M, et al.: Evidence for 2-Methoxyestradiol-mediated inhibition of receptor tyrosine kinase RON in the management of prostate cancer. Int J Mol Sci 22, https://doi.org/10.3390/ijms22041852, 2021. – reference: Alhakamy NA, Ahmed OA, Fahmy UA, et al.: Development and in vitro evaluation of 2-Methoxyestradiol loaded polymeric micelles for enhancing anticancer activities in prostate cancer. Polymers (Basel) 13, https://doi.org/10.3390/polym13060884, 2021. – reference: Thompson PA, Shields PG, Freudenheim JL, et al.: Genetic polymorphisms in catechol-O-methyltransferase, menopausal status, and breast cancer risk. Cancer Res 58, 2107-2110, 1998. – reference: Sasaki M, Kaneuchi M, Sakuragi N, et al.: Multiple promoters of catechol-O-methyltransferase gene are selectively inactivated by CpG hypermethylation in endometrial cancer. Cancer Res 63, 3101-3106, 2003. – reference: Liehr JG: Dual role of estrogens as hormones and pro-carcinogens: tumour initiation by metabolic activation of estrogens. Eur J Cancer Prev 6, 3-10, 1997. – reference: Fabian MR, Sonenberg N and Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem 79, 351-379, 2010. |
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| Title | Association between catechol-O-methyltransferase expression and the prognosis of prostate cancer |
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