Diagnostic potential of hypermethylation of the cysteine dioxygenase 1 gene (CDO1) promoter DNA in pancreatic cancer. Issue 9 (10th August 2019)

• Record Type: Journal Article
• Authors: Nishizawa, Nobuyuki; Harada, Hiroki; Kumamoto, Yusuke; Kaizu, Takashi; Katoh, Hiroshi; Tajima, Hiroshi; Ushiku, Hideki; Yokoi, Keigo; Igarashi, Kazuharu; Fujiyama, Yoshiki; Okuwaki, Kosuke; Iwai, Tomohisa; Watanabe, Masahiko; Yamashita, Keishi
• Is Part Of: Cancer science. Volume 110:Issue 9(2019)
• Page Start: 2846
• Page End: 2855
• Publication Date: 2019-08-10
• Subjects: CDO1 -- diagnosis -- methylation -- pancreatic cancer -- prognosis; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.14134
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: DNA markers for pancreatic ductal adenocarcinoma (PDAC) are urgently needed for detection of minimally invasive disease. The epigenetic relevance of the cysteine dioxygenase 1 gene ( CDO1 ) has been never investigated in PDAC. Three studies, including cellular experiments, tissue validation, and pilot testing for pancreatic cytology, were carried out. Promoter DNA methylation value (MV) of CDO1 was quantified by quantitative methylation‐specific PCR. CDO1 expression was consistent with its promoter DNA methylation in 7 PDAC cell lines. In 160 retrospectively collected primary PDAC tumor tissues, MV was significantly higher compared to the corresponding noncancerous pancreas (area under the receiver operating characteristic curve [AUC] = 0.97, P < .0001), and CDO1 hypermethylation was highly specific to PDAC tumor tissues. CDO1 hypermethylation group (MV over 19) was significantly associated with diverse prognostic factors in PDAC. Surprisingly, it was significantly higher in prospectively collected PDAC cytology samples (n = 37), including both pancreatic juice (n = 12) and endoscopic ultrasound‐fine needle aspiration (EUS‐FNA) cytology (n = 25) compared to pancreatic benign diseases (AUC = 0.96, P < .0001). Detection of PDAC was confirmed by DNA testing in 35 of 37 patients (95% sensitivity); thus, it was more sensitive than cytology (33%) or EUS‐FNA cytology (88%). Promoter DNA methylation of CDO1 is extremely specific for PDAC tumors, and accumulates with PDAC tumor progression. It could be a definitive diagnostic marker of PDAC in pancreatic juice or EUS‐FNA cytology. Abstract : CDO1 methylation is extremely specific for pancreatic ductal adenocarcinoma in pancreatic cytology samples. CDO1 methylation could be a definitive diagnostic marker of pancreatic ductal adenocarcinoma.