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

• Published in: The Journal of pathology Vol. 222; no. 3; pp. 310 - 319
• Main Authors: Tchernitsa, Oleg, Kasajima, Atsuko, Schäfer, Reinhold, Kuban, Ralf-Jürgen, Ungethüm, Ute, Györffy, Balazs, Neumann, Ulf, Simon, Eva, Weichert, Wilko, Ebert, Matthias PA, Röcken, Christoph
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.11.2010; Wiley
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Dicer; Disease Progression; Drosha; Female; Gastric cancer; Gastroenterology. Liver. Pancreas. Abdomen; Gene expression; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Humans; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; lymph node metastases; Lymph nodes; Lymphatic Metastasis; Male; Medical sciences; Metastases; MicroRNAs - metabolism; Middle Aged; miRNA; Neoplasm Proteins - metabolism; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Polymerase chain reaction; Probes; Prognosis; Reverse Transcriptase Polymerase Chain Reaction - methods; Ribonuclease III - metabolism; RNA, Neoplasm - metabolism; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survival; Survival Analysis; Tumors; Evaluation; RNA interference; Prognosis; Dicer; gastric cancer; Micro RNA; Malignant lymphadenopathy; Malignant hemopathy; Malignant tumor; Stomach cancer; Drosha; Lymph node metastasis; Gene silencing; Anatomic pathology; Messenger RNA; Tumor progression; Digestive diseases; miRNA; lymph node metastases; Cancer; Gastric disease
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2759

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[trade mark sign] 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. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.