Diagnosis of pancreatic neoplasms using a novel method of DNA methylation analysis of mucin expression in pancreatic juice

Seiya Yokoyama, Sho Kitamoto, Michiyo Higashi, Yuko Goto, Taro Hara, Dai Ikebe, Taketo Yamaguchi, Yoshifumi Arisaka, Toru Niihara, Hiroto Nishimata, Sadao Tanaka, Kyoichi Takaori, Surinder Kumar Batra, Suguru Yonezawa

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs). Our immunohistochemistry (IHC) studies have shown a consensus position on mucin expression profiles in pancreatic neoplasms as follows: MUC1-positive but MUC2-negative expression in PDACs; MUC1-negative but MUC2-positive expression in intestinal-type IPMNs (dangerous type); MUC1-negative and MUC2-negative expression in gastric-type IPMNs (safe type); High MUC4 expression in PDAC patients with a poor outcome; and MUC4-positive expression in intestinal-type IPMNs. We also showed that three mucin genes (MUC1, MUC2 and MUC4) expression in cancer cell line was regulated by DNA methylation. We have developed a novel 'methylation-specific electrophoresis (MSE)' method to analyze the DNA methylation status of mucin genes by high sensitivity and resolution. By using the MSE method, we evaluated pancreatic juice samples from 45 patients with various pancreatic lesions. The results were compared with final diagnosis of the pancreatic lesions including IHC of mucin expression in the paired pancreatic tissues. The results indicated that the DNA methylation status of MUC1, MUC2 and MUC4 in pancreatic juice matched with the mucin expression in tissue. Analyses of the DNA methylation status of MUC1, MUC2 and MUC4 were useful for differential diagnosis of human pancreatic neoplasms, with specificity and sensitivity of 87% and 80% for PDAC; 100% and 88% for intestinal-type IPMN; and 88% and 77% for gastric-type IPMN, respectively. In conclusion, MSE analysis of human pancreatic juice may provide useful information for selection of treatment for pancreatic neoplasms.

Original languageEnglish (US)
Article numbere93760
JournalPloS one
Volume9
Issue number4
DOIs
StatePublished - Apr 8 2014

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pancreatic juice
Pancreatic Juice
pancreatic neoplasms
mucins
Mucins
DNA methylation
DNA Methylation
Pancreatic Neoplasms
neoplasms
Methylation
Electrophoresis
adenocarcinoma
Neoplasms
methylation
electrophoresis
lesions (animal)
Genes
immunohistochemistry
methodology
Tissue

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Yokoyama, S., Kitamoto, S., Higashi, M., Goto, Y., Hara, T., Ikebe, D., ... Yonezawa, S. (2014). Diagnosis of pancreatic neoplasms using a novel method of DNA methylation analysis of mucin expression in pancreatic juice. PloS one, 9(4), [e93760]. https://doi.org/10.1371/journal.pone.0093760

Diagnosis of pancreatic neoplasms using a novel method of DNA methylation analysis of mucin expression in pancreatic juice. / Yokoyama, Seiya; Kitamoto, Sho; Higashi, Michiyo; Goto, Yuko; Hara, Taro; Ikebe, Dai; Yamaguchi, Taketo; Arisaka, Yoshifumi; Niihara, Toru; Nishimata, Hiroto; Tanaka, Sadao; Takaori, Kyoichi; Batra, Surinder Kumar; Yonezawa, Suguru.

In: PloS one, Vol. 9, No. 4, e93760, 08.04.2014.

Research output: Contribution to journalArticle

Yokoyama, S, Kitamoto, S, Higashi, M, Goto, Y, Hara, T, Ikebe, D, Yamaguchi, T, Arisaka, Y, Niihara, T, Nishimata, H, Tanaka, S, Takaori, K, Batra, SK & Yonezawa, S 2014, 'Diagnosis of pancreatic neoplasms using a novel method of DNA methylation analysis of mucin expression in pancreatic juice', PloS one, vol. 9, no. 4, e93760. https://doi.org/10.1371/journal.pone.0093760
Yokoyama, Seiya ; Kitamoto, Sho ; Higashi, Michiyo ; Goto, Yuko ; Hara, Taro ; Ikebe, Dai ; Yamaguchi, Taketo ; Arisaka, Yoshifumi ; Niihara, Toru ; Nishimata, Hiroto ; Tanaka, Sadao ; Takaori, Kyoichi ; Batra, Surinder Kumar ; Yonezawa, Suguru. / Diagnosis of pancreatic neoplasms using a novel method of DNA methylation analysis of mucin expression in pancreatic juice. In: PloS one. 2014 ; Vol. 9, No. 4.
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abstract = "Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs). Our immunohistochemistry (IHC) studies have shown a consensus position on mucin expression profiles in pancreatic neoplasms as follows: MUC1-positive but MUC2-negative expression in PDACs; MUC1-negative but MUC2-positive expression in intestinal-type IPMNs (dangerous type); MUC1-negative and MUC2-negative expression in gastric-type IPMNs (safe type); High MUC4 expression in PDAC patients with a poor outcome; and MUC4-positive expression in intestinal-type IPMNs. We also showed that three mucin genes (MUC1, MUC2 and MUC4) expression in cancer cell line was regulated by DNA methylation. We have developed a novel 'methylation-specific electrophoresis (MSE)' method to analyze the DNA methylation status of mucin genes by high sensitivity and resolution. By using the MSE method, we evaluated pancreatic juice samples from 45 patients with various pancreatic lesions. The results were compared with final diagnosis of the pancreatic lesions including IHC of mucin expression in the paired pancreatic tissues. The results indicated that the DNA methylation status of MUC1, MUC2 and MUC4 in pancreatic juice matched with the mucin expression in tissue. Analyses of the DNA methylation status of MUC1, MUC2 and MUC4 were useful for differential diagnosis of human pancreatic neoplasms, with specificity and sensitivity of 87{\%} and 80{\%} for PDAC; 100{\%} and 88{\%} for intestinal-type IPMN; and 88{\%} and 77{\%} for gastric-type IPMN, respectively. In conclusion, MSE analysis of human pancreatic juice may provide useful information for selection of treatment for pancreatic neoplasms.",
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AU - Yokoyama, Seiya

AU - Kitamoto, Sho

AU - Higashi, Michiyo

AU - Goto, Yuko

AU - Hara, Taro

AU - Ikebe, Dai

AU - Yamaguchi, Taketo

AU - Arisaka, Yoshifumi

AU - Niihara, Toru

AU - Nishimata, Hiroto

AU - Tanaka, Sadao

AU - Takaori, Kyoichi

AU - Batra, Surinder Kumar

AU - Yonezawa, Suguru

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N2 - Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasms (IPMNs). Our immunohistochemistry (IHC) studies have shown a consensus position on mucin expression profiles in pancreatic neoplasms as follows: MUC1-positive but MUC2-negative expression in PDACs; MUC1-negative but MUC2-positive expression in intestinal-type IPMNs (dangerous type); MUC1-negative and MUC2-negative expression in gastric-type IPMNs (safe type); High MUC4 expression in PDAC patients with a poor outcome; and MUC4-positive expression in intestinal-type IPMNs. We also showed that three mucin genes (MUC1, MUC2 and MUC4) expression in cancer cell line was regulated by DNA methylation. We have developed a novel 'methylation-specific electrophoresis (MSE)' method to analyze the DNA methylation status of mucin genes by high sensitivity and resolution. By using the MSE method, we evaluated pancreatic juice samples from 45 patients with various pancreatic lesions. The results were compared with final diagnosis of the pancreatic lesions including IHC of mucin expression in the paired pancreatic tissues. The results indicated that the DNA methylation status of MUC1, MUC2 and MUC4 in pancreatic juice matched with the mucin expression in tissue. Analyses of the DNA methylation status of MUC1, MUC2 and MUC4 were useful for differential diagnosis of human pancreatic neoplasms, with specificity and sensitivity of 87% and 80% for PDAC; 100% and 88% for intestinal-type IPMN; and 88% and 77% for gastric-type IPMN, respectively. In conclusion, MSE analysis of human pancreatic juice may provide useful information for selection of treatment for pancreatic neoplasms.

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