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大学・研究所にある論文を検索できる 「Clinicopathological impacts of DNA methylation alterations on pancreatic ductal adenocarcinoma : prediction of early recurrence based on genome-wide DNA methylation profiling (本文)」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

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

遠藤, 泰 慶應義塾大学

2021.09.21

概要

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 Infnium HumanMethylation450 BeadChip, and DNA methylation quantifcation was verifed 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-fxed parafn-embedded T samples from 34 patients in a validation cohort.

Results: The DNA methylation profles of N samples tended to difer from those of C samples, and 91,907 probes showed signifcant diferences in DNA methylation levels between C and T samples. Epigenetic clustering of T samples was signifcantly correlated with a larger tumor diameter and early recurrence (ER), defned as relapse within 6 months after surgery. Three marker CpG sites, applicable to formalin-fxed parafn-embedded surgically resected materials regardless of their tumor cell content, were identifed for prediction of ER. The sensitivity and specifcity 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 fndings 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.

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