論文

査読有り
2019年2月

Identification of marker genes and pathways specific to precancerous duodenal adenomas and early stage adenocarcinomas.

Journal of gastroenterology
  • Yoshiki Sakaguchi
  • ,
  • Nobutake Yamamichi
  • ,
  • Shuta Tomida
  • ,
  • Chihiro Takeuchi
  • ,
  • Natsuko Kageyama-Yahara
  • ,
  • Yu Takahashi
  • ,
  • Kazuya Shiogama
  • ,
  • Ken-Ichi Inada
  • ,
  • Masao Ichinose
  • ,
  • Mitsuhiro Fujishiro
  • ,
  • Kazuhiko Koike

54
2
開始ページ
131
終了ページ
140
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00535-018-1489-4

BACKGROUND: The mechanism behind the pathogenesis and carcinogenesis of these neoplasms is not fully understood. The objective of this study was to identify genetic markers and pathways specific to precancerous duodenal adenomas and early stage adenocarcinomas through gene expression analysis. METHODS: Gene expression profiling was performed in 4 pairs of duodenal adenoma/adenocarcinomas and corresponding matched normal tissue. Genes with consistent expression differences were identified and confirmed in 7 independent pairs. Gene set enrichment analysis (GSEA) was performed to characterize gene expression profiles of duodenal adenoma/adenocarcinomas, together with immunohistochemical staining of candidate oncogenic genes. RESULTS: 626 probes consistently demonstrated over a twofold expression difference between tumor-normal pairs. Reverse transcriptase polymerase chain reaction of genes with the most prominent difference in expression between tumors and normal mucosa (KLK7, KLK6, CEMIP, MMP7, KRT17, LGR5, G6PC, S100G, APOA1) validated the results of gene expression analysis. GSEA demonstrated a strong association between duodenal adenoma/adenocarcinomas with colorectal adenomas (p < 10-5) and gene expression patterns seen after APC gene knockout (p < 10-5), suggesting that the Wnt/β-catenin pathway plays a crucial role in the carcinogenesis of these neoplasms. Immunohistochemical staining of an independent group of duodenal adenomas confirmed over-accumulation of β-catenin in 80.0% (16/20). CONCLUSIONS: Precancerous duodenal adenomas and early stage adenocarcinomas demonstrate gene expression characteristics with a strong resemblance to colorectal adenomas. The results of this study strongly suggest that upregulation of the Wnt/β-catenin pathway is the major factor involved in the initial stages of the carcinogenesis of duodenal adenocarcinomas.

リンク情報
DOI
https://doi.org/10.1007/s00535-018-1489-4
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29951927

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