Systematic evaluation of the miRNA-ome and its downstream effects on mRNA expression identifies gastric cancer progression

Oleg Tchernitsa, Atsuko Kasajima, Reinhold Schäfer, Ralf Jürgen Kuban, Ute Ungethüm, Balazs Györffy, Ulf Neumann, Eva Simon, Wilko Weichert, Matthias P.A. Ebert, Christoph Röcken

Research output: Contribution to journalArticlepeer-review

105 Citations (Scopus)

Abstract

We investigated the differential expression of Dicer and Drosha, as well as that of microRNA (miRNA), in adjacent normal and tumour samples of patients with gastric cancer. The expression of Dicer and Drosha was studied by immunohistochemistry in 332 gastric cancers and correlated with clinico-pathological patient characteristics. Differential expression of miRNAs was studied using the Invitrogen NCode Multi-Species miRNA Microarray Probe Set containing 857 mammalian probes in a test set of six primary gastric cancers (three with and three without lymph node metastases). Differential expression was validated by RT-PCR on an independent validation set of 20 patients with gastric cancer. Dicer and Drosha were differentially expressed in non-neoplastic and neoplastic gastric tissue. The expression of Drosha correlated with local tumour growth and was a significant independent prognosticator of patient survival. Twenty miRNAs were up-and two down-regulated in gastric carcinoma compared with non-neoplastic tissue. Six of these miRNAs separated node-positive from node-negative gastric cancers, ie miR-103, miR-21, miR-145, miR-106b, miR-146a, and miR-148a. Five miRNAs expressed differentially in node-positive cancers had conserved binding sites for mRNAs differentially expressed in the same set of tumour samples. Gastric cancer shows a complex derangement of the miRNA-ome, including Dicer and Drosha. These changes correlate independently with patient prognosis and probably influence local tumour growth and nodal spread.

Original languageEnglish
Pages (from-to)310-319
Number of pages10
JournalJournal of Pathology
Volume222
Issue number3
DOIs
Publication statusPublished - 2010 Nov

Keywords

  • Dicer
  • Drosha
  • Gastric cancer
  • Lymph node metastases
  • MiRNA
  • Prognosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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