Epigenetic Inactivation of Protocadherin 10 by Methylation in Colorectal Cancer
Aberrant promoter methylation of CpG islands of tumor-suppressor genes has been recognized as one of the important tumor markers for cancer detection. The aim of this study was to investigate the promoter methylation status of protocadherin 10 (PCDH10), a tumor suppressor gene, in Iranian colorectal cancer (CRC) patients. Cancerous and the adjacent normal tissues obtained from 38 CRC patients were used to assess the methylation status of PCDH10 with Methylation Specific PCR, in addition, to study the expression level of this gene by quantitative PCR. The relationship between hypermethylation and the demographic characteristics of these patients was analyzed. The promoter methylation level of PCDH10 was statistically different between tumoral and normal tissues in CRC patients. Twenty-seven out of 38 patients showed hypermethylation with a sensitivity of 73% and a specificity of 97%. PCDH10 expression decreased in 15 cases (46%) as 16 cases (50 %) showed overexpression and 1 case (4%) had no changes. Not a significant association was reported between PCDH10 hypermethylation and the clinicopathological characteristics (P>0.05). Our results indicated that PCDH10 methylation has a critical function in CRC, with a nearly elevated sensitivity and a high specificity in the Iranian population, qualify it as a potential candidate biomarker.
Javadzade SH, Reisi M, Mostafavi F, Hasanzade A, Shahnazi H, Sharifirad G. Factors associated with the fecal occult blood testing for colorectal cancer screening based on health belief model structures in moderate risk individuals, Isfahan, 2011. Journal of education and health promotion. 2012;1.
Kerachian MA, Kerachian M. Long interspersed nucleotide element-1 (LINE-1) methylation in colorectal cancer. Clinica chimica acta; international journal of clinical chemistry. 2019;488:209-14.
Mousavi SM, Gouya MM, Ramazani R, Davanlou M, Hajsadeghi N, Seddighi Z. Cancer incidence and mortality in Iran. Annals of oncology : official journal of the European Society for Medical Oncology. 2009;20(3):556-63.
Dolatkhah R, Somi MH, Bonyadi MJ, Asvadi Kermani I, Farassati F, Dastgiri S. Colorectal cancer in Iran: molecular epidemiology and screening strategies. Journal of cancer epidemiology. 2015;2015.
Hessami Arani S, Kerachian MA. Rising rates of colorectal cancer among younger Iranians: is diet to blame? Current oncology (Toronto, Ont). 2017;24(2):e131-e7.
Markowitz SD, Dawson DM, Willis J, Willson JK. Focus on colon cancer. Cancer cell. 2002;1(3):233-6.
Bosch LJ, Carvalho B, Fijneman RJ, Jimenez CR, Pinedo HM, Van Engeland M, et al. Molecular tests for colorectal cancer screening. Clinical colorectal cancer. 2011;10(1):8-23.
Barati Bagerabad M, Tavakolian S, Abbaszadegan MR, Kerachian MA. Promoter Hypermethylation of the Eyes Absent 4 Gene is a Tumor-Specific Epigenetic Biomarker in Iranian Colorectal Cancer Patients. Acta medica Iranica. 2018;56(1):21-7.
Binefa G, Rodríguez-Moranta F, Teule À, Medina-Hayas M. Colorectal cancer: from prevention to personalized medicine. World journal of gastroenterology: WJG. 2014;20(22):6786.
Rokni P, Shariatpanahi AM, Sakhinia E, Kerachian MA. BMP3 promoter hypermethylation in plasma-derived cell-free DNA in colorectal cancer patients. Genes & genomics. 2018;40(4):423-8.
Bond JH. Fecal occult blood test screening for colorectal cancer. Gastrointestinal endoscopy clinics of North America. 2002;12(1):11-21.
Mojtabanezhad Shariatpanahi A, Yassi M, Nouraie M, Sahebkar A, Varshoee Tabrizi F, Kerachian MA. The importance of stool DNA methylation in colorectal cancer diagnosis: A meta-analysis. PLoS One. 2018;13(7):e0200735.
Nishiumi S, Kobayashi T, Ikeda A, Yoshie T, Kibi M, Izumi Y, et al. A novel serum metabolomics-based diagnostic approach for colorectal cancer. PloS one. 2012;7(7):e40459.
Bardhan K, Liu K. Epigenetics and colorectal cancer pathogenesis. Cancers. 2013;5(2):676-713.
Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010;31(1):27-36.
Shivapurkar N, Gazdar A. DNA methylation based biomarkers in non-invasive cancer screening. Current molecular medicine. 2010;10(2):123-32.
Dong Y, Zhao H, Li H, Li X, Yang S. DNA methylation as an early diagnostic marker of cancer. Biomedical reports. 2014;2(3):326-30.
Narayan G, Xie D, Freddy AJ, Ishdorj G, Do C, Satwani P, et al. PCDH10 promoter hypermethylation is frequent in most histologic subtypes of mature lymphoid malignancies and occurs early in lymphomagenesis. Genes, Chromosomes and Cancer. 2013;52(11):1030-41.
Wang L, Xie P-G, Lin Y-L, Ma J-G, Li W-P. Aberrant methylation of PCDH10 predicts worse biochemical recurrence-free survival in patients with prostate cancer after radical prostatectomy. Medical science monitor: international medical journal of experimental and clinical research. 2014;20:1363.
Tang X, Yin X, Xiang T, Li H, Li F, Chen L, et al. Protocadherin 10 is frequently downregulated by promoter methylation and functions as a tumor suppressor gene in non-small cell lung cancer. Cancer Biomarkers. 2013;12(1):11-9.
Li Z, Chim JC, Yang M, Ye J, Wong BC, Qiao L. Role of PCDH10 and its hypermethylation in human gastric cancer. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2012;1823(2):298-305.
Lin Y-L, Li Z-G, Guan T-Y. The clinical significance of PCDH10 promoter methylation in patients with bladder transitional cell carcinoma. Urologia internationalis. 2013;90(2):219-24.
Zhong X, Zhu Y, Mao J, Zhang J, Zheng S. Frequent epigenetic silencing of PCDH10 by methylation in human colorectal cancer. Journal of cancer research and clinical oncology. 2013;139(3):485-90.
Nollet F, Kools P, Van Roy F. Phylogenetic analysis of the cadherin superfamily allows identification of six major subfamilies besides several solitary members. Journal of molecular biology. 2000;299(3):551-72.
Angst BD, Marcozzi C, Magee AI. The cadherin superfamily: diversity in form and function. Journal of cell science. 2001;114(4):629-41.
Hulpiau P, van Roy F. New insights into the evolution of metazoan cadherins. Molecular biology and evolution. 2011;28(1):647-57.
Wolverton T, Lalande M. Identification and characterization of three members of a novel subclass of protocadherins. Genomics. 2001;76(1):66-72.
Pourhoseingholi MA, Fazeli Z, Ashtari S, Bavand-Pour FSF. Mortality trends of gastrointestinal cancers in Iranian population. Gastroenterology and hepatology from bed to bench. 2013;6(Suppl 1):S52.
Dolatkhah R, Dastgiri S, Somi MH, Bonyadi MJ, Gherami S, Fotouhi N, et al. Common KRAS and BRAF Mutations in Colorectal Cancer Patients. Govaresh. 2015;20(1):27-33.
Carmona FJ, Azuara D, Berenguer-Llergo A, Fernández AF, Biondo S, de Oca J, et al. DNA methylation biomarkers for noninvasive diagnosis of colorectal cancer. Cancer prevention research. 2013.
Ying J, Li H, Seng TJ, Langford C, Srivastava G, Tsao S, et al. Functional epigenetics identifies a protocadherin PCDH10 as a candidate tumor suppressor for nasopharyngeal, esophageal and multiple other carcinomas with frequent methylation. Oncogene. 2006;25(7):1070.
Jao TM, Tsai MH, Lio HY, Weng WT, Chen CC, Tzeng ST, et al. Protocadherin 10 suppresses tumorigenesis and metastasis in colorectal cancer and its genetic loss predicts adverse prognosis. International journal of cancer. 2014;135(11):2593-603.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.