Summary
In order to demonstrate the relationship between methylation of fragile histidine triad (FHIT) and T-cadherin/H-cadherin (CDH13) genes and liver cancer, the methylation status of FHIT and CDH13 was detected in healthy individuals and in Mongolian and Han patients with liver cancer. The phenol-chloroform method was used to extract genomic DNA. The methylation specific polymerase chain reaction method was applied to detect the methylation status of FHIT and CDH13. The relationship between smoking and alcohol consumption and gene (FHIT and CDH13) methylation was analyzed. There was significant difference in methylation rate of FHIT (72.67%, 34.67%) and CDH13 (72.0%, 28.0%) between liver cancer patients and healthy individuals of Mongolian descent (P<0.05), as well as that of FHIT (68%, 30.67%) and CDH13 (64%, 26%) between liver cancer patients and healthy individuals of Han individuals (P<0.05). There was also a relationship between smoking and drinking and the methylation of FHIT and CDH13 (P<0.05). Thus, the methylation of FHIT and CDH13 had a relationship with liver cancer incidence. Smoking and alcohol ingestion may promote the methylation of FHIT and CDH13.
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Chiang JK, Chih WL, Kao YH. Effect of ultrasonography surveillance in patients with liver cancer: a population-based longitudinal study. BMJ Open, 2017, 7(6):e015936
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CACancer J Clin, 2016, 66(2): 115–132
Zhang QB, Meng XT, Jia QA, et al. Herbal compound songyou yin and moderate swimming suppress growth and metastasis of liver cancer by enhancing immune function. Integr Cancer Ther, 2016, 15(3): 368–375
Karpf AR. Epigenomic reactivation screening to identify genes silenced by DNA hypermethylation in human cancer. Curr Opin Mol Ther, 2007, 9(3): 231–241
Huang QB, Zhang HW, Liao ZB. Carboxypeptidase A6 Promotes the Proliferation and Migration of Hepatocellular Carcinoma by Up-regulating AKT Signaling Pathway. Curr Med Sci, 2019, 39(5): 727–733
Zhao BB, Ye ZH, Gao X, et al. Diwu Yanggan Modulates the Wnt/p-catenin Pathway and Inhibits Liver Carcinogenesis Signaling in 2-AAF/PH Model Rats. Curr Med Sci, 2019, 39(6): 913–919
Wang Q, Pan LH, Lin L, et al. Essential Oil from Carpesium abrotanoides L. Induces Apoptosis via Activating Mitochondrial Pathway in Hepatocellular Carcinoma Cells. Curr Med Sci, 2018, 38(6): 1045–1053
Li Q, Ding L, Jing N, et al. Folate deficiency and aberrant DNAmethylation and expression of FHIT gene were associated with cervical pathogenesis. Oncol Lett, 2018, 15(2): 1963–1972
Druck T, Hadaczek P, Fu TB, et al. Structure and expression of the human FHIT gene in normal and tumor cells. Cancer Res, 1997, 57(3): 504–512
Sirnes S, Honne H, Ahmed D, et al. DNA methylation analyses of the connexin gene family reveal silencing of GJC1 (Connexin45) by promoter hypermethylation in colorectal cancer. Epigenetics, 2011, 6(5): 602–609
Hibi K, Kodera Y, Ito K, et al. Methylation pattern of CDH13 gene in digestive tract cancers. Br J Cancer, 2004, 91: 1139–1142
Lin YL, Xie PG, Ma JG. Aberrantmethylation of CDH13 is a potential biomarker for predicting the recurrence and progression of non muscle invasive bladder cancer. Med Sci Momt, 2014, 20: 1572–1577
Ren JZ, Huo JR. Correlation between T-cadherin gene expression and aberrant methylation of T-cadherin promoter in human colon carcinoma cells. Med Oncol, 2012, 29(2): 915–918
Widschwendter A, Ivarsson L, Blassnig A, et al. CDH1 and CDH13 methylation in serum is an independent prognostic marker in cervical cancer patients. Int J Cancer, 2004, 109(2): 163–166
Yang J, Niu H, Huang Y, et al. A systematic analysis of the relationship of CDH13 promoter methylation and breast cancer risk and prognosis. PLoS One, 2016, 11(5):e0149185
Wang Y, Zhang L, Yang J, et al. CDH13 promoter methylation regulates cisplatin resistance of non-small cell lung cancer cells. Oncol Lett, 2018, 16(5): 1139–1143
Zhong YH, Peng H, Cheng HZ, et al. Quantitative assessment of the diagnostic role of CDH13 promoter methylation in lung cancer. Asian Pac J Cancer Prev, 2015, 16(3): 1139–1143
Kochl S, Niederstatter H, Parson W. DNA extraction and quantitation of forensic samples using the phenol-chloroform method and real-time PCR. In: Carracedo A, ed. Forensic DNA Typing Protocols. Methods in Molecular Biology. Totowa, NJ, USA: Humana Press, 2005:13–29.
Szumilas M. Explaining odds ratios. J Can Acad Child Adolesc Psychiatry, 2010, 19(3): 3–227
McKillop IH, Schrum LW. Alcohol and liver cancer. Alcohol, 2005, 35(3): 195–203
Shanmugham JR, Zavras Al, Rosner BA, et al. Alcohol-folate interactions in the risk of oral cancer in women: a prospective cohort study. Cancer Epidemiol Prev Biomarkers, 2010, 19(10): 2516–2524
Lee YCA, Cohet C, Yang YC, et al. Meta-analysis of epidemiologic studies on cigarette smoking and liver cancer. Int J Epidemiol, 2009, 38(6): 1497–1511
Qi JJ, Wen J, Zhang LY, et al. Correlation between diabetes and smoking index and benign prostatic hyperplasia. Shandong Med J (Chinese), 2010, 50(39): 3–5
Ohta M, Inoue H, Cotticelli MG, et al. The FHIT gene, spanning the chromosome 3pl4.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Cell, 1996, 84(4): 587–597
Ranscht B, Dours Zimmermann MT. T-cadherin, a novel cadherin cell adhesion molecule in the nervous system lacks the conserved cytoplasmic region. Neuron, 1991, 7(3): 391–402
Lister R, Pelizzola M, Dowen RH, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature, 2009, 462(7271): 315–322
Zhu C, Feng X, Ye G, et al. Meta-analysis of possible role of cadherin gene methylation in evolution and prognosis of hepatocellular carcinoma with a PRISMA guideline. Medicine, 2017, 96(16):e6650
Bird A. DNA methylation patterns and epigenetic memory. Genes Dev, 2002, 16: 6–21
Jones PA, Buckley JD. The role of DNA methylation in cancer. Adv Cancer Res, 1990, 54: 1–23
Su Y, Wang X, Li J, et al. The clinicopathological significance and drug target potential of FHIT in breast cancer, a meta-analysis and literature review. Drug Des Devel Ther, 2015, 2015(9): 5439–5445
Kuroki T, Trapasso F, Yendamuri S, et al. Allele loss and promoter hypermethylation of VHL, RAR-beta, RASSF1A, and FHIT tumor suppressor genes on chromosome 3p in esophageal squamous cell carcinoma. Cancer Res, 2003, 63(3): 3724–3728
Drilon A, Sugita H, Sima CS, et al. A prospective study of tumor suppressor gene methylation as a prognostic biomarker in surgically resected stage I to IIIA non-small-cell lung cancers. J Thorac Oncol, 2014, 9(9): 1272–1277
Konishi K, Watanabe Y, Shen L, et al. DNA methylation profiles of primary colorectal carcinoma and matched liver metastasis. PLoS One, 2011, 6:e27889
Moelans CB, de Groot JS, Pan X, et al. Clonal intratumor heterogeneity of promoter hypermethylation in breast cancer by MS-MLPA. Mod Pathol, 2014, 27: 869–874
Tahara T, Maegawa S, Chung W, et al. Examination of whole blood DNA methylation as a potential risk marker for gastric cancer. Cancer Prev Res (Phila), 2013, 6(10): 1093–1100
Jin Z, Cheng Y, Olaru A, et al. Promoter hypermethylation of CDH13 is a common, early event inhuman esophageal adenocarcinogenesis and correlates with clinical risk factors. Int J Cancer, 2008, 123(10) 2331–2336
Chen F, Huang T, Ren Y, et al. Clinical significance of CDH 13 promoter methylation as a biomarker for bladder cancer: a meta-analysis. BMC Urol, 2016, 16:52
Chen YC. Arsenic methylation and bladder cancer risk in Taiwan. Cancer Causes Control, 2003, 14(4): 303–310
Friedrich MG. Detection of methylated apoptosis-associated genes in urine sediments of bladder cancer patients. Clin Cancer Res, 2004, 10(22): 7457–7465
Maruyama R, Toyooka S, Toyooka KO, et al. Aberrant promoter methylation profile of bladder cancer and its relationship to clinicopathological features. Cancer Res, 2001, 61(24): 8659–8663
Zhang H, Nie W, Huang F. The correlation relationship between P14ARF gene DNA methylation and primary liver cancer. Med Sci Momt, 2015, 21: 3077–3082
Hibi K, Nakayama H, Kodera Y, et al. CDH13 promoter region is specifically methylated in poorly differentiated colorectal cancer. Br J Cancer, 2004, 90: 1030–1033
Maruyama R, Sugio K, Yoshino I, et al. Hypermethylation of FHIT as a prognostic marker in non-small cell lung carcinoma. Cancer, 2004, 100(7): 1472–1477
Ryerson AB, Eheman CR, Altekruse SF, et al. Annual report to the nation on the status of cancer, 1975–2012, featuring the increasing incidence of liver cancer. Cancer, 2016, 122(9): 1312–1337
Liang H, Wang J, Xiao H, et al. Estimation of cancer incidence and mortality attributable to alcohol drinking in China. BMC Pub Health, 2010, 10:730
Lin Z, Luo M, Chen X, et al. Combined detection of plasma ZIC1, HOXD10 and RUNX3 methylation is a promising strategy for early detection of gastric cancer and precancerous lesions. J Cancer, 2017, 8(6): 1038–1044
Klootwijk R, Groenen P, Schijvenaars M, et al. Genetic variants in ZIC1, ZIC2, and ZIC3 are not major risk factors for neural tube defects in humans. Am J Med Genet A, 2004, 124(1):40–47
Shah V, Drill E, Lance-Jones C. Ectopic expression of HoxdlO in thoracic spinal segments induces motoneurons with a lumbosacral molecular profile and axon projections to the limb. DevDyn, 2004, 231(1): 1–43
Yamamoto H, Ito K, Kawai M, et al. Runx3 expression during mouse tongue and palate development. Anat Rec A Discov Mol Cell Evol Biol, 2006, 288(7): 695–699
Zhang C, Yu W, Wang L, et al. DNA methylation analysis of the SHOX2 and RASSF1A panel m bronchoalveolar lavage fluid for lung cancer diagnosis. J Cancer, 2017, 8(17): 3585–3591
Zhu ZZ, Bao LL, Zhao K, et al. Copy Number Aberrations of Multiple Genes Identified as Prognostic Markers for Extrahepatic Metastasis-free Survival of Patients with Hepatocellular Carcinoma. Curr Med Sci, 2019, 39(5): 759–765
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The authors declare that they have no conflict of interest. All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Inner Mongolia Medical University and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
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This work was supported by grants from the Major Scientific Project of the Affiliated Hospital of Inner Mongolia Medical University (No. NYFY ZD009) and National Natural Science Foundation of China (No. 81760676).
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Tuoya, Ad., Wang, Dx., Xing, Ys. et al. Relationship between Methylation of FHIT and CDH13 Gene Promoter Region and Liver Cancer. CURR MED SCI 40, 502–509 (2020). https://doi.org/10.1007/s11596-020-2202-4
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DOI: https://doi.org/10.1007/s11596-020-2202-4