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

Tchernitsa, O; Kasajima, A; Schäfer, R; Kuban, RJ; Ungethüm, U; Györffy, B; Neumann, U; Simon, E; Weichert, W; Ebert, MP; Röcken, C

doi:10.1002/path.2759

2010

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Document type:: Journal Article; Research Support, Non-U.S. Gov't; Article
Author(s):: Tchernitsa, O; Kasajima, A; Schäfer, R; Kuban, RJ; Ungethüm, U; Györffy, B; Neumann, U; Simon, E; Weichert, W; Ebert, MP; Röcken, C
Title:: Systematic evaluation of the miRNA-ome and its downstream effects on mRNA expression identifies gastric cancer progression.
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((TM)) 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. «
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((TM)) Multi-Species miRNA Microarray Probe Set containing 857 mammalian probes in a test set o... »
Journal title abbreviation:: J Pathol
Year:: 2010
Journal volume:: 222
Journal issue:: 3
Pages contribution:: 310-9
Language:: eng
Fulltext / DOI:: doi:10.1002/path.2759
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/20726036
Print-ISSN:: 0022-3417
TUM Institution:: II. Medizinische Klinik und Poliklinik (Gastroenterologie)
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Innere Medizin II, Gastroenterologie (Prof. Schmid)2010