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(™) 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.
authors: Institute of Pathology, Charité University Hospital, Berlin, Germany.
authors: Oleg
authors: O
authors: Tchernitsa
authors: Atsuko
authors: A
authors: Kasajima
authors: Reinhold
authors: R
authors: Schäfer
authors: Ralf-Jürgen
authors: RJ
authors: Kuban
authors: Ute
authors: U
authors: Ungethüm
authors: Balazs
authors: B
authors: Györffy
authors: Ulf
authors: U
authors: Neumann
authors: Eva
authors: E
authors: Simon
authors: Wilko
authors: W
authors: Weichert
authors: Matthias P A
authors: MP
authors: Ebert
authors: Christoph
authors: C
authors: Röcken
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism; D011379:Prognosis; D012334:RNA, Neoplasm / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D043244:Ribonuclease III / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis
chemical_list: D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C517918:DROSHA protein, human; D043244:Ribonuclease III