Research progress of DNA methylation and cholangiocarcinoma_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIN Fabin ¹ ,  QIU Funan ^1,2

1. Provincial Clinical Medical College, Fujian Medical University, Fuzhou 350001, P. R. China;
2. Department of Hepatobiliary Surgery, Fujian Provincial Hospital, Fuzhou 350001, P. R. China;

Corresponding author：

QIU Funan, Email: qiufunan72@163.com

Keywords：

DNA methylation; cholangiocarcinoma; review

DOI：

10.7507/1007-9424.201812063

Video：

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Objective To explore the role of DNA methylation in the pathogenesis of cholangiocarcinoma and its progress as a therapeutic target for cholangiocarcinoma.Method The relevant literatures at home and abroad in recent years about the DNA methylation and cholangiocarcinoma were reviewed.Results Methylation is a frequent event in cholangiocarcinoma and effect the occurrence and development of cholangiocarcinogenesis. DNA methylation inhibitors reactivate tumor suppressor genes.Conclusions DNA methylation is closely related to the cholangiocarcinogenesis. Despite there is no effective clinical therapeutics and diagnosis at present, with further study, DNA methylation is expected to be one of the new target to treatment and diagnosis this disease.

Citation： LIN Fabin, QIU Funan. Research progress of DNA methylation and cholangiocarcinoma. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(7): 870-875. doi: 10.7507/1007-9424.201812063 Copy

1.	Rizvi S, Khan SA, Hallemeier CL, et al. Cholangiocarcinoma-evolving concepts and therapeutic strategies. Nat Rev Clin Oncol, 2017, 15(2): 95-111.
2.	Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology, 2013, 145(6): 1215-1229.
3.	Endo I, Gonen M, Yopp AC, et al. Intrahepatic cholangi-ocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg, 2008, 248(1): 84-96.
4.	Donato F, Gelatti U, Tagger A, et al. Intrahepatic cholangi-ocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case-control study in Italy. Cancer Causes Control, 2001, 12(10): 959-964.
5.	El-Serag HB, Engels EA, Landgren O, et al. Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population‐based study of U. S. veterans. Hepatology, 2009, 49(1): 116-123.
6.	Lee TY, Lee SS, Jung SW, et al. Hepatitis B virus infection and intrahepatic cholangiocarcinoma in Korea: a case-control study. Am J Gastroenterol, 2008, 103(7): 1716-1720.
7.	Zhou Y, Yin ZJ, Li B, et al. Risk factors for intrahepatic cholan-giocarcinoma: A case-control study in China. World J Gastroenterol, 2008, 14(4): 249-253.
8.	Sithithaworn P, Yongvanit P, Duenngai K, et al. Roles of liver fluke infection as risk factor for cholangiocarcinoma. J Hepatobiliary Pancreat Sci, 2014, 21(5): 301-308.
9.	Ayé Soukhathammavong P, Rajpho V, Phongluxa K, et al. Subtle to severe hepatobiliary morbidity in Opisthorchis viverrini endemic settings in southern Laos. Acta Trop, 2015, 141(Pt B): 303-309.
10.	Blechacz B, Komuta M, Roskams T, et al. Clinical diagnosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol, 2011, 8(9): 512-522.
11.	Yang B, House MG, Guo M, et al. Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma. Mod Pathol, 2005, 18(3): 412-420.
12.	Shen J, Wang S, Zhang YJ, et al. Genome-wide DNA methylation profiles in hepatocellular carcinoma. Hepatology, 2012, 55(6): 1799-1808.
13.	Botling J, Edlund K, Lohr M, et al. Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis, and tissue microarray validation. Clin Cancer Res, 2013, 19(1): 194-204.
14.	Hur K, Cejas P, Feliu J, et al. Hypomethylation of long interspersed nuclear element-1 (LINE-1) leads to activation of proto-oncogenes in human colorectal cancer metastasis. Gut, 2014, 63(4): 635-646.
15.	Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol, 1987, 196(2): 261-282.
16.	Strathdee G, Davies BR, Vass JK, et al. Cell type-specific methylation of an intronic CpG island controls expression of the MCJ gene. Carcinogenesis, 2004, 25(5): 693-701.
17.	Brenet F, Moh M, Funk P, et al. DNA methylation of the first exon is tightly linked to transcriptional silencing. PloS One, 2011, 6(1): e14524.
18.	Lister R, Pelizzola M, Dowen RH, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature, 2009, 462(7271): 315-322.
19.	Lee S, Kim WH, Jung HY, et al. Aberrant CpG island methylation of multiple genes in intrahepatic cholangiocarcinoma. Am J Pathol, 2002, 161(3): 1015-1022.
20.	Borger DR, Tanabe KK, Fan KC, et al. Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist, 2012, 17(1): 72-79.
21.	Kipp BR, Voss JS, Kerr SE, et al. Isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma. Human Pathology, 2012, 43(10): 1552-1558.
22.	Xu W, Yang H, Liu Y, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell, 2011, 19(1): 17-30.
23.	薛立新, 李可洲. 胆管癌相关基因甲基化研究进展. 中国普外基础与临床杂志, 2011, 18(6): 672-675.
24.	张恬莹, 兰涛, 魏玲玲, 等. 甲基化在肝纤维化过程中的作用及其机制的研究进展. 中国普外基础与临床杂志, 2019, 26(2): 229-235.
25.	Kaur P, Mani S, Cros MP, et al. Epigenetic silencing of sFRP1 activates the canonical Wnt pathway and contributes to increased cell growth and proliferation in hepatocellular carcinoma. Tumour Biol, 2012, 33(2): 325-336.
26.	Cheng W, Qi Y, Tian L, et al. Dicer promotes tumorigenesis by translocating to nucleus to promote SFRP1 promoter methylation in cholangiocarcinoma cells. Cell death Dis, 2017, 8(2): e2628.
27.	Amornpisutt R, Proungvitaya S, Jearanaikoon P, et al. DNA methylation level of OPCML and SFRP1: a potential diagnostic biomarker of cholangiocarcinoma. Tumor Biology, 2015, 36(7): 4973-4978.
28.	Brait MM, Ling SS, Nagpal JK, et al. Cysteine dioxygenase 1 is a tumor suppressor gene silenced by promoter methylation in multiple human cancers. Plos One, 2012, 7(9): e44951.
29.	Yamashita K, Waraya M, Kim MS, et al. Detection of methylated CDO1 in plasma of colorectal cancer; a PCR study. Plos One, 2014, 9(12): e113546.
30.	Igarashi K, Yamashita K, Katoh H, et al. Prognostic significance of promoter DNA hypermethylation of the cysteine dioxygenase 1 (CDO1) gene in primary gallbladder cancer and gallbladder disease. PloS One, 2017, 12(11): e0188178.
31.	Ushiku H, Yamashita K, Ema A, et al. DNA diagnosis of peritoneal fluid cytology test by CDO1 promoter DNA hypermethylation in gastric cancer. Gastric Cancer, 2017, 20(5): 784-792.
32.	Nakamoto S, Kumamoto Y, Igarashi K, et al. Methylated promoter DNA of CDO1 gene and preoperative serum CA19-9 are prognostic biomarkers in primary extrahepatic cholangiocarcinoma. PLoS One, 2018, 13(10): e0205864.
33.	Zhang L, Zhang Q, Li L, et al. DLEC1, a 3p tumor suppressor, represses NF-κB signaling and is methylated in prostate cancer. J Mol Med (Berl), 2015, 93(6): 691-701.
34.	Seng TJ, Currery N, Cooper WA, et al. DLEC1 and MLH1 promoter methylation are associated with poor prognosis in non-small cell lung carcinoma. Br J Cancer, 2008, 99(2): 375-382.
35.	Kim Y, Lee K, Jeong S, et al. DLEC1 methylation is associated with a better clinical outcome in patients with intrahepatic cholangiocarcinoma of the small duct subtype. Virchows Arc, 2019 Jan 4. [Epub ahead of print].
36.	Peters I, Eggers H, Atschekzei F, et al. GATA5 CpG island methylation in renal cell cancer: a potential biomarker for metastasis and disease progression. BJU Int, 2012, 110(2 Pt 2): E144-E152.
37.	Guo M, Akiyama Y, House MG, et al. Hypermethylation of the GATA Genes in Lung Cancer. Clin Cancer Res, 2004, 10(23): 7917-7924.
38.	Akiyama Y, Watkins N, Suzuki H, et al. GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer. Mol Cell Biol, 2003, 23(23): 8429-8439.
39.	Liu P, Zhou TF, Qiu BA, et al. Methylation-Mediated Silencing of GATA5 Gene Suppresses Cholangiocarcinoma Cell Proliferation and Metastasis. Transl Oncol, 2018, 11(3): 585-592.
40.	Cheng JC, Yoo CB, Weisenberger DJ, et al. Preferential response of cancer cells to zebularine. Cancer Cell, 2004, 6(2): 151-158.
41.	Nakamura K, Nakabayashi K, Htet Aung K, et al. DNA methyltransferase inhibitor zebularine induces human cholangiocarcinoma cell death through alteration of DNA methylation status. PloS One, 2015, 10(3): e0120545.
42.	Socco S, Bovee RC, Palczewski MB, et al. Epigenetics: the third pillar of nitric oxide signaling. Pharmacol Res, 2017, 121: 52-58.
43.	Spirlì C, Fabris L, Duner F, et al. Cytokine-stimulated nitric oxide production inhibits adenylyl cyclase and cAMP-dependent secretion in cholangiocytes. Gastroenterology, 2003, 124(3): 737-753.
44.	Sorkin A. Internalization of the epidermal growth factor receptor: role in signalling. Biochem Soc Trans, 2001, 29(Pt 4): 480-484.
45.	Prachayakul V, Kanchanapermpoon J, Thuwajit C, et al. DNA methylation markers improve the sensitivity of endoscopic retrograde cholangiopancreatography-based brushing cytology in extrahepatic cholangiocarcinoma. Technol Cancer Res Treat, 2017, 16(6): 1252-1258.
46.	Shin SH, Lee K, Kim BH, et al. Bile-based detection of extrahepatic cholangiocarcinoma with quantitative DNA methylation markers and its high sensitivity. J Mol Diagn, 2012, 14(3): 256-263.

1. Rizvi S, Khan SA, Hallemeier CL, et al. Cholangiocarcinoma-evolving concepts and therapeutic strategies. Nat Rev Clin Oncol, 2017, 15(2): 95-111.
2. Rizvi S, Gores GJ. Pathogenesis, diagnosis, and management of cholangiocarcinoma. Gastroenterology, 2013, 145(6): 1215-1229.
3. Endo I, Gonen M, Yopp AC, et al. Intrahepatic cholangi-ocarcinoma: rising frequency, improved survival, and determinants of outcome after resection. Ann Surg, 2008, 248(1): 84-96.
4. Donato F, Gelatti U, Tagger A, et al. Intrahepatic cholangi-ocarcinoma and hepatitis C and B virus infection, alcohol intake, and hepatolithiasis: a case-control study in Italy. Cancer Causes Control, 2001, 12(10): 959-964.
5. El-Serag HB, Engels EA, Landgren O, et al. Risk of hepatobiliary and pancreatic cancers after hepatitis C virus infection: A population‐based study of U. S. veterans. Hepatology, 2009, 49(1): 116-123.
6. Lee TY, Lee SS, Jung SW, et al. Hepatitis B virus infection and intrahepatic cholangiocarcinoma in Korea: a case-control study. Am J Gastroenterol, 2008, 103(7): 1716-1720.
7. Zhou Y, Yin ZJ, Li B, et al. Risk factors for intrahepatic cholan-giocarcinoma: A case-control study in China. World J Gastroenterol, 2008, 14(4): 249-253.
8. Sithithaworn P, Yongvanit P, Duenngai K, et al. Roles of liver fluke infection as risk factor for cholangiocarcinoma. J Hepatobiliary Pancreat Sci, 2014, 21(5): 301-308.
9. Ayé Soukhathammavong P, Rajpho V, Phongluxa K, et al. Subtle to severe hepatobiliary morbidity in Opisthorchis viverrini endemic settings in southern Laos. Acta Trop, 2015, 141(Pt B): 303-309.
10. Blechacz B, Komuta M, Roskams T, et al. Clinical diagnosis and staging of cholangiocarcinoma. Nat Rev Gastroenterol Hepatol, 2011, 8(9): 512-522.
11. Yang B, House MG, Guo M, et al. Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma. Mod Pathol, 2005, 18(3): 412-420.
12. Shen J, Wang S, Zhang YJ, et al. Genome-wide DNA methylation profiles in hepatocellular carcinoma. Hepatology, 2012, 55(6): 1799-1808.
13. Botling J, Edlund K, Lohr M, et al. Biomarker discovery in non-small cell lung cancer: integrating gene expression profiling, meta-analysis, and tissue microarray validation. Clin Cancer Res, 2013, 19(1): 194-204.
14. Hur K, Cejas P, Feliu J, et al. Hypomethylation of long interspersed nuclear element-1 (LINE-1) leads to activation of proto-oncogenes in human colorectal cancer metastasis. Gut, 2014, 63(4): 635-646.
15. Gardiner-Garden M, Frommer M. CpG islands in vertebrate genomes. J Mol Biol, 1987, 196(2): 261-282.
16. Strathdee G, Davies BR, Vass JK, et al. Cell type-specific methylation of an intronic CpG island controls expression of the MCJ gene. Carcinogenesis, 2004, 25(5): 693-701.
17. Brenet F, Moh M, Funk P, et al. DNA methylation of the first exon is tightly linked to transcriptional silencing. PloS One, 2011, 6(1): e14524.
18. Lister R, Pelizzola M, Dowen RH, et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature, 2009, 462(7271): 315-322.
19. Lee S, Kim WH, Jung HY, et al. Aberrant CpG island methylation of multiple genes in intrahepatic cholangiocarcinoma. Am J Pathol, 2002, 161(3): 1015-1022.
20. Borger DR, Tanabe KK, Fan KC, et al. Frequent mutation of isocitrate dehydrogenase (IDH)1 and IDH2 in cholangiocarcinoma identified through broad-based tumor genotyping. Oncologist, 2012, 17(1): 72-79.
21. Kipp BR, Voss JS, Kerr SE, et al. Isocitrate dehydrogenase 1 and 2 mutations in cholangiocarcinoma. Human Pathology, 2012, 43(10): 1552-1558.
22. Xu W, Yang H, Liu Y, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Cancer Cell, 2011, 19(1): 17-30.
23. 薛立新, 李可洲. 胆管癌相关基因甲基化研究进展. 中国普外基础与临床杂志, 2011, 18(6): 672-675.
24. 张恬莹, 兰涛, 魏玲玲, 等. 甲基化在肝纤维化过程中的作用及其机制的研究进展. 中国普外基础与临床杂志, 2019, 26(2): 229-235.
25. Kaur P, Mani S, Cros MP, et al. Epigenetic silencing of sFRP1 activates the canonical Wnt pathway and contributes to increased cell growth and proliferation in hepatocellular carcinoma. Tumour Biol, 2012, 33(2): 325-336.
26. Cheng W, Qi Y, Tian L, et al. Dicer promotes tumorigenesis by translocating to nucleus to promote SFRP1 promoter methylation in cholangiocarcinoma cells. Cell death Dis, 2017, 8(2): e2628.
27. Amornpisutt R, Proungvitaya S, Jearanaikoon P, et al. DNA methylation level of OPCML and SFRP1: a potential diagnostic biomarker of cholangiocarcinoma. Tumor Biology, 2015, 36(7): 4973-4978.
28. Brait MM, Ling SS, Nagpal JK, et al. Cysteine dioxygenase 1 is a tumor suppressor gene silenced by promoter methylation in multiple human cancers. Plos One, 2012, 7(9): e44951.
29. Yamashita K, Waraya M, Kim MS, et al. Detection of methylated CDO1 in plasma of colorectal cancer; a PCR study. Plos One, 2014, 9(12): e113546.
30. Igarashi K, Yamashita K, Katoh H, et al. Prognostic significance of promoter DNA hypermethylation of the cysteine dioxygenase 1 (CDO1) gene in primary gallbladder cancer and gallbladder disease. PloS One, 2017, 12(11): e0188178.
31. Ushiku H, Yamashita K, Ema A, et al. DNA diagnosis of peritoneal fluid cytology test by CDO1 promoter DNA hypermethylation in gastric cancer. Gastric Cancer, 2017, 20(5): 784-792.
32. Nakamoto S, Kumamoto Y, Igarashi K, et al. Methylated promoter DNA of CDO1 gene and preoperative serum CA19-9 are prognostic biomarkers in primary extrahepatic cholangiocarcinoma. PLoS One, 2018, 13(10): e0205864.
33. Zhang L, Zhang Q, Li L, et al. DLEC1, a 3p tumor suppressor, represses NF-κB signaling and is methylated in prostate cancer. J Mol Med (Berl), 2015, 93(6): 691-701.
34. Seng TJ, Currery N, Cooper WA, et al. DLEC1 and MLH1 promoter methylation are associated with poor prognosis in non-small cell lung carcinoma. Br J Cancer, 2008, 99(2): 375-382.
35. Kim Y, Lee K, Jeong S, et al. DLEC1 methylation is associated with a better clinical outcome in patients with intrahepatic cholangiocarcinoma of the small duct subtype. Virchows Arc, 2019 Jan 4. [Epub ahead of print].
36. Peters I, Eggers H, Atschekzei F, et al. GATA5 CpG island methylation in renal cell cancer: a potential biomarker for metastasis and disease progression. BJU Int, 2012, 110(2 Pt 2): E144-E152.
37. Guo M, Akiyama Y, House MG, et al. Hypermethylation of the GATA Genes in Lung Cancer. Clin Cancer Res, 2004, 10(23): 7917-7924.
38. Akiyama Y, Watkins N, Suzuki H, et al. GATA-4 and GATA-5 transcription factor genes and potential downstream antitumor target genes are epigenetically silenced in colorectal and gastric cancer. Mol Cell Biol, 2003, 23(23): 8429-8439.
39. Liu P, Zhou TF, Qiu BA, et al. Methylation-Mediated Silencing of GATA5 Gene Suppresses Cholangiocarcinoma Cell Proliferation and Metastasis. Transl Oncol, 2018, 11(3): 585-592.
40. Cheng JC, Yoo CB, Weisenberger DJ, et al. Preferential response of cancer cells to zebularine. Cancer Cell, 2004, 6(2): 151-158.
41. Nakamura K, Nakabayashi K, Htet Aung K, et al. DNA methyltransferase inhibitor zebularine induces human cholangiocarcinoma cell death through alteration of DNA methylation status. PloS One, 2015, 10(3): e0120545.
42. Socco S, Bovee RC, Palczewski MB, et al. Epigenetics: the third pillar of nitric oxide signaling. Pharmacol Res, 2017, 121: 52-58.
43. Spirlì C, Fabris L, Duner F, et al. Cytokine-stimulated nitric oxide production inhibits adenylyl cyclase and cAMP-dependent secretion in cholangiocytes. Gastroenterology, 2003, 124(3): 737-753.
44. Sorkin A. Internalization of the epidermal growth factor receptor: role in signalling. Biochem Soc Trans, 2001, 29(Pt 4): 480-484.
45. Prachayakul V, Kanchanapermpoon J, Thuwajit C, et al. DNA methylation markers improve the sensitivity of endoscopic retrograde cholangiopancreatography-based brushing cytology in extrahepatic cholangiocarcinoma. Technol Cancer Res Treat, 2017, 16(6): 1252-1258.
46. Shin SH, Lee K, Kim BH, et al. Bile-based detection of extrahepatic cholangiocarcinoma with quantitative DNA methylation markers and its high sensitivity. J Mol Diagn, 2012, 14(3): 256-263.

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Research progress of DNA methylation and cholangiocarcinoma

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