1. Dual epigenetic changes in diabetes mellitus‐associated pancreatic ductal adenocarcinoma correlate with downregulation of E‐cadherin and worsened prognosis
- Author
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Yutaro Hara, Hiroki Mizukami, Keisuke Yamazaki, Takahiro Yamada, Akiko Igawa, Yuki Takeuchi, Takanori Sasaki, Hanae Kushibiki, Kotaro Murakami, Kazuhiro Kudoh, Keinosuke Ishido, and Kenichi Hakamada
- Subjects
diabetes mellitus ,pancreatic ductal adenocarcinoma ,promoter methylation ,microRNA ,E‐cadherin ,Pathology ,RB1-214 - Abstract
Abstract Diabetes mellitus (DM) is a risk factor for pancreatic ductal adenocarcinoma (PDAC) that promotes the promoter methylation of CDH1. It is still unclear whether DM can exert other epigenetic effects, such as altering microRNA (miR) expression, in PDAC. The expression of miR‐100‐5p is known to be changed in DM patients and can suppress the expression of E‐cadherin. In this study, the correlation between DM status and dual epigenetic changes was evaluated in PDAC specimens from patients who underwent radical surgical resection. A total of 132 consecutive patients with PDAC were clinicopathologically evaluated. E‐cadherin and nuclear β‐catenin expression was measured using immunohistochemistry. DNA and miRs were extracted from the main tumor site on formalin‐fixed paraffin‐embedded tissue sections. TaqMan miR assays were applied to assess miR‐100‐5p expression. Bisulfite modification was conducted on the extracted DNA, which was then subjected to methylation‐specific polymerase chain reaction. Immunohistochemistry revealed that decreased E‐cadherin expression and increased nuclear β‐catenin expression were significantly associated with DM and poor tumor cell differentiation. The presence of long‐duration DM (≥3 years) was a significant factor contributing to CDH1 promoter methylation (p < 0.01), while miR‐100‐5p expression was proportionally correlated with the preoperative HbA1c level (R = 0.34, p
- Published
- 2023
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