Clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma: prediction of early recurrence based on genome-wide DNA methylation profiling

Yutaka Endo, Mao Fujimoto, Nanako Ito, Yoriko Takahashi, Minoru Kitago, Masahiro Gotoh, Nobuyoshi Hiraoka, Teruhiko Yoshida, Yuko Kitagawa, Yae Kanai, Eri Arai

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Purpose: The present study was conducted to clarify the clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma (PDAC). Methods: Genome-wide DNA methylation screening was performed using the Infinium HumanMethylation450 BeadChip, and DNA methylation quantification was verified using pyrosequencing. We analyzed fresh-frozen tissues from an initial cohort (17 samples of normal control pancreatic tissue [C] from 17 patients without PDAC, and 34 samples of non-cancerous pancreatic tissue [N] and 82 samples of cancerous tissue [T] both obtained from 82 PDAC patients) and formalin-fixed paraffin-embedded T samples from 34 patients in a validation cohort. Results: The DNA methylation profiles of N samples tended to differ from those of C samples, and 91,907 probes showed significant differences in DNA methylation levels between C and T samples. Epigenetic clustering of T samples was significantly correlated with a larger tumor diameter and early recurrence (ER), defined as relapse within 6 months after surgery. Three marker CpG sites, applicable to formalin-fixed paraffin-embedded surgically resected materials regardless of their tumor cell content, were identified for prediction of ER. The sensitivity and specificity for detection of patients belonging to the ER group using a panel combining these three marker CpG sites, including a CpG site in the CDK14 gene, were 81.8% and 71.7% and 88.9% and 70.4% in the initial and validation cohorts, respectively. Conclusion: These findings indicate that DNA methylation alterations may have a clinicopathological impact on PDAC. Application of our criteria will ultimately allow prediction of ER after surgery to improve the outcome of PDAC patients.

Original languageEnglish
Pages (from-to)1341-1354
Number of pages14
JournalJournal of Cancer Research and Clinical Oncology
Volume147
Issue number5
DOIs
Publication statusPublished - 2021 May

Keywords

  • DNA methylation
  • Ductal adenocarcinoma
  • Early recurrence
  • Infinium assay
  • Pancreas

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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