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06.03.2020 | Translational Research and Biomarkers

Promoter DNA Hypermethylation of the Cysteine Dioxygenase 1 (CDO1) Gene in Intraductal Papillary Mucinous Neoplasm (IPMN)

verfasst von: Yoshiki Fujiyama, MD, Yusuke Kumamoto, MD, PhD, Nobuyuki Nishizawa, MD, PhD, Shuji Nakamoto, MD, Hiroki Harada, MD, Kazuko Yokota, MD, Yoko Tanaka, MD, Kazuharu Igarashi, MD, PhD, Hironobu Oiki, MD, Kosuke Okuwaki, MD, PhD, Tomohisa Iwai, MD, PhD, Sabine Kajita, MD, PhD, Hiroyuki Takahashi, MD, PhD, Hiroshi Tajima, MD, Takashi Kaizu, MD, PhD, Jiichiro Sasaki, MD, PhD, Masahiko Watanabe, MD, PhD, FACS, Keishi Yamashita, MD, PhD, FACS

Erschienen in: Annals of Surgical Oncology | Ausgabe 10/2020

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Abstract

Background

Intraductal papillary mucinous neoplasm (IPMN) involves adenoma (IPMA), a precancerous lesion, cancer (IPMC) including high-grade dysplasia (HGD), and invasive carcinoma (IC). DNA markers of IPMN are required for detection of invasive disease, and cysteine dioxygenase 1 (CDO1) gene promoter hypermethylation is a potential candidate. However, it has never been investigated in the context of IPMN.

Patients and Methods

A total of 107 IPMN tumor tissues, including 41 IPMC and 66 IPMA, were studied. CDO1 promoter methylation was quantified using TaqMan quantitative methylation-specific polymerase chain reaction (qMSP) in patients with IPMN and other pancreatic cystic disorders after pancreatectomy.

Results

The methylation values (TaqMeth Vs) of CDO1 increased when noncancerous pancreas tissues were compared with IPMA and HGD (p < 0.0001). Among IPMC, the TaqMeth Vs in IC were not significantly higher than in HGD. The TaqMeth Vs of the solid tumors were higher than those of the cystic tumors (p = 0.0016), which were in turn higher than the corresponding noncancerous tissues (p < 0.0001). Prognostic analysis revealed that high TaqMeth Vs (≥ 14.1) resulted in a poorer prognosis than low TaqMeth Vs (< 14.1) (p < 0.0001). In other pancreatic cystic diseases, only malignant mucinous cystic neoplasm showed DNA hypermethylation of its promoter. A pilot study in pancreatic juice confirmed methylation in all IPMN samples but not in benign pancreatic diseases (p = 0.0277).

Conclusions

CDO1 promoter hypermethylation is extremely specific to IPMN and may accumulate with IPMN tumor progression during the adenoma–carcinoma sequence. It might be a promising candidate as a diagnostic marker of pancreatic cystic diseases.

Fernandez-del Castillo C, Adsay NV (2010) Intraductal papillary mucinous neoplasms of the pancreas. Gastroenterology 139: 708–713.PubMed

Tanaka M, Chari S, Adsay V, et al. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology 2006; 6: 17–32.PubMed

Okabayashi T, Kobayashi M, Nishimori I, et al. Clinicopathological features and medical management of intraductal papillary mucinous neoplasms. J Gastroenterol Hepatol 2006; 21: 462–467.PubMed

Yopp AC, Katabi N, Janakos M, et al. Invasive carcinoma arising in intraductal papillary mucinous neoplasms of the pancreas: a matched control study with conventional pancreatic ductal adenocarcinoma. Ann Surg 2011; 253: 968–974.PubMed

Mino-Kenudson M, Fernandez-del Castillo C, Baba Y, et al. Prognosis of invasive intraductal papillary mucinous neoplasm depends on histological and precursor epithelial subtypes. Gut 2011; 60: 1712–1720.PubMedPubMedCentral

Wilson GC, Maithel SK, Bentrem D, et al. Are the current guidelines for the surgical management of intraductal papillary mucinous neoplasms of the pancreas adequate? a multi-institutional study. J Am Coll Surg 2017; 224: 461–469.PubMed

Shin SH, Han DJ, Park KT, et al. Validating a simple scoring system to predict malignancy and invasiveness of intraductal papillary mucinous neoplasms of the pancreas. World J Surg 2010; 34: 776–783.PubMed

Hwang DW, Jang JY, Lee SE, et al. Clinicopathologic analysis of surgically proven intraductal papillary mucinous neoplasms of the pancreas in SNUH: a 15-year experience at a single academic institution. Langenbecks Arch Surg 2012; 397: 93–102.PubMed

Kim JR, Jang JY, Kang MJ, et al. Clinical implication of serum carcinoembryonic antigen and carbohydrate antigen 19-9 for the prediction of malignancy in intraductal papillary mucinous neoplasm of pancreas. J Hepatobil Pancreat Sci 2015; 22: 699–707.

10.

Wu J, Matthaei H, Maitra A, et al. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med 2011; 3: 92ra66.PubMedPubMedCentral

11.

Takano S, Fukasawa M, Maekawa S, et al. Deep sequencing of cancer-related genes revealed GNAS mutations to be associated with intraductal papillary mucinous neoplasms and its main pancreatic duct dilation. PLoS One 2014; 9: e98718.PubMedPubMedCentral

12.

Tamura K, Ohtsuka T, Ideno N, et al. Treatment strategy for main duct intraductal papillary mucinous neoplasms of the pancreas based on the assessment of recurrence in the remnant pancreas after resection: a retrospective review. Ann Surg 2014; 259: 360–368.

13.

Kuboki Y, Shimizu K, Hatori T, et al. Molecular biomarkers for progression of intraductal papillary mucinous neoplasm of the pancreas. Pancreas 2015; 44: 227–235.PubMed

14.

Sato N, Goggins M. Epigenetic alterations in intraductal papillary mucinous neoplasms of the pancreas. J Hepatobil Pancreat Surg 2006; 13: 280–285.

15.

Yamashita K, Upadhyay S, Osada M, et al. Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in esophageal squamous cell carcinoma. Cancer Cell 2002; 2(6): 485–95.

16.

Yamashita K, Hosoda K, Nishizawa N, et al. Epigenetic biomarkers of promoter DNA methylation in the new era of cancer treatment. Cancer Sci 2018; 109: 3695–3706.PubMedPubMedCentral

17.

Adsay NV, Fukushima N, Furukawa T, et al. Intraductal neoplasm of the pancreas. In: Bosman FT, Carneiro F, Hruban RH, Theise ND, editors. WHO Classification of Tumors of Digestive System. Lyon. IARC Press 2010; 304–313.

18.

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: e0205864.PubMedPubMedCentral

19.

Yamashita K, Waraya M, Kim MS, et al. Detection of methylated CDO1 in plasma of colorectal cancer; a PCR study. PLoS One 2014; 9: e113546.PubMedPubMedCentral

20.

Kojima K, Nakamura T, Ooizumi Y, et al. Clinical significance of cancer specific methylation of the CDO1 gene in small bowel cancer. PLoS One 2019; 14: e0211108.PubMedPubMedCentral

21.

Ushiku H, Yamashita K, Katoh H, et al. Promoter DNA methylation of CDO1 gene and its clinical significance in esophageal squamous cell carcinoma. Dis Esoph 2017; 30: 1-9.

22.

Minatani N, Waraya M, Yamashita K, et al. Prognostic significance of promoter DNA hypermethylation of cysteine dioxygenase 1 (CDO1) gene in primary breast cancer. PLoS One 2016; 11: e0144862.PubMedPubMedCentral

23.

Ooki A, Maleki Z, Tsay JJ, et al. A panel of novel detection and prognostic methylated DNA markers in primary non-small cell lung cancer and serum DNA. Clin Cancer Res 2017; 23: 7141-7152.PubMed

24.

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: 784–792.PubMed

25.

Kojima K, Nakamura T, Ohbu M, et al. Cysteine dioxygenase type 1 (CDO1) gene promoter methylation during the adenoma-carcinoma sequence in colorectal cancer. PLoS One 2018; 13: e0194785.PubMedPubMedCentral

26.

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: e0188178.PubMedPubMedCentral

27.

Deckers IA, Schouten LJ, Van Neste L, et al. Promoter methylation of CDO1 identifies clear-cell renal cell cancer patients with poor survival outcome. Clin Cancer Res 2015; 21: 3492–3500.PubMedPubMedCentral

28.

Huang RL, Su PH, Liao YP, et al. Integrated epigenomics analysis reveals a DNA methylation panel for endometrial cancer detection using cervical scrapings. Clin Cancer Res 2017; 23: 263–272.PubMed

29.

Brait M, Ling S, Nagpal JK, et al. Cysteine dioxygenase 1 is a tumor suppressor gene silenced by promoter methylation in multiple human cancers. PLoS One 2012; 7: e44951.PubMedPubMedCentral

30.

Meller S, Zipfel L, Gevensleben H, et al. CDO1 promoter methylation is associated with gene silencing and is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients. Epigenetics 2016; 11: 871–880.PubMedPubMedCentral

31.

Nishizawa N, Harada H, Kumamoto Y, et al. Diagnostic potential of hypermethylation of the cysteine dioxygenase 1 gene (CDO1) promoter DNA in pancreatic cancer. Cancer Sci 2019; 110(9): 2846–2855.PubMedPubMedCentral

32.

Kojima K, Minatani N, Ushiku H, et al. Prediction of onset of remnant gastric cancer by promoter DNA methylation of CDO1/HOPX/Reprimo/E-cadherin. Oncotarget 2019; 10: 2423–2434.PubMedPubMedCentral

33.

Furukawa T, Hatori T, Fujita I, et al. Prognostic relevance of morphological types of intraductal papillary mucinous neoplasms of the pancreas. Gut 2011; 60: 509–516.PubMed

34.

Distler M, Kersting S, Niedergethmann M et al, Pathohistological subtype predicts survival in patients with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. Ann Surg 2013; 258: 324–330.PubMed

35.

Kargozaran H, Vu V, Ray P, et al. Invasive IPMN and MCN: same organ, different outcomes? Ann Surg Oncol 2011; 18: 345–351.PubMed

36.

Cone MM, Rea JD, Diggs BS, et al. Predicting malignant intraductal papillary mucinous neoplasm: a single-center review. Am J Surg 2011; 201: 575–579.PubMed

37.

Tanaka M, Fernandez-del Castillo C, Adsay V, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology 2012; 12: 183–197.PubMed

38.

Passot G, Lebeau R, Hervieu V, et al. Recurrences after surgical resection of intraductal papillary mucinous neoplasm of the pancreas: a single-center study of recurrence predictive factors. Pancreas 2012; 41: 137–141.PubMed

39.

Nara S, Onaya H, Hiraoka N, et al. Preoperative evaluation of invasive and noninvasive intraductal papillary-mucinous neoplasms of the pancreas: clinical, radiological, and pathological analysis of 123 cases. Pancreas 2009; 38: 8–16.PubMed

40.

Shimizu Y, Kanemitsu Y, Sano T, et al. A nomogram for predicting the probability of carcinoma in patients with intraductal papillary-mucinous neoplasm. World J Surg 2010; 34: 2932–2938.PubMed

41.

Shimizu Y, Yamaue H, Maguchi H, et al. Predictors of malignancy in intraductal papillary mucinous neoplasm of the pancreas: analysis of 310 pancreatic resection patients at multiple high-volume centers. Pancreas 2013; 42: 883–888.PubMed

42.

Correa-Gallego C, Do R, Lafemina J, et al. Predicting dysplasia and invasive carcinoma in intraductal papillary mucinous neoplasms of the pancreas: development of a preoperative nomogram. Ann Surg Oncol 2013; 20: 4348–4355.PubMed

43.

Hijioka S, Shimizu Y, Mizuno N, et al. Can long-term follow-up strategies be determined using a nomogram-based prediction model of malignancy among intraductal papillary mucinous neoplasms of the pancreas? Pancreas 2014; 43: 367–372.PubMed

Titel: Promoter DNA Hypermethylation of the Cysteine Dioxygenase 1 (CDO1) Gene in Intraductal Papillary Mucinous Neoplasm (IPMN)
verfasst von: Yoshiki Fujiyama, MD
Yusuke Kumamoto, MD, PhD
Nobuyuki Nishizawa, MD, PhD
Shuji Nakamoto, MD
Hiroki Harada, MD
Kazuko Yokota, MD
Yoko Tanaka, MD
Kazuharu Igarashi, MD, PhD
Hironobu Oiki, MD
Kosuke Okuwaki, MD, PhD
Tomohisa Iwai, MD, PhD
Sabine Kajita, MD, PhD
Hiroyuki Takahashi, MD, PhD
Hiroshi Tajima, MD
Takashi Kaizu, MD, PhD
Jiichiro Sasaki, MD, PhD
Masahiko Watanabe, MD, PhD, FACS
Keishi Yamashita, MD, PhD, FACS
Publikationsdatum: 06.03.2020
Verlag: Springer International Publishing
Erschienen in: Annals of Surgical Oncology / Ausgabe 10/2020
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-020-08291-2

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Promoter DNA Hypermethylation of the Cysteine Dioxygenase 1 (CDO1) Gene in Intraductal Papillary Mucinous Neoplasm (IPMN)