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- W1981927724 abstract "Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CAPurpose:Our aim was to investigate whether microRNAs can predict the clinical outcome of patients with gastric cancer (GC). We used integrated analysis of microRNA and mRNA expression profiles to identify GC microRNA subtypes and their underlying regulatory scenarios.Experimental Design:MicroRNA-based GC subtypes were identified by consensus clustering analysis of microRNA profiles of 90 GC tissues. Activated pathways in the subtypes were identified by gene expression profiles. Further integrated analysis was performed to model a microRNA regulatory network for each subtype. RNA and protein expression were analyzed by RT-PCR and tissue microarray, respectively, in a cohort of 385 GC cases (including the 90 cases for profiling) to validate the key microRNAs and targets in the network. Both in vitro and in vivo experiments were performed to further validate the findings.Results:MicroRNA profiles of 90 GC cases identified two microRNA subtypes significantly associated with survival. The poor-prognosis GC microRNA subtype was characterized by overexpression of epithelial-to-mesenchymal transition (EMT) markers. This GC “mesenchymal subtype” was further validated in a patient cohort comprising 385 cases. Integrated analysis identified a key microRNA regulatory network likely driving the GC mesenchymal subtype. Three of the microRNAs (miR-200c, miR-200b, and miR-125b) targeting the most genes in the network were significantly associated with survival. Functional experiments demonstrated that miR-200b suppressed ZEB1, augmented E-cadherin, inhibited cell migration, and suppressed tumor growth in a mouse model.Conclusions: We have uncovered a key microRNA regulatory network that defines the mesenchymal GC subtype significantly associated with poor overall survival in GC.Citation Format: Fengju Song, Kexin Chen. Integrated microRNA network analyses identify a poor prognosis subtype of gastric cancer characterized by the miR-200 family. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1474. doi:10.1158/1538-7445.AM2014-1474" @default.
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- W1981927724 date "2014-09-30" @default.
- W1981927724 modified "2023-09-26" @default.
- W1981927724 title "Abstract 1474: Integrated microRNA network analyses identify a poor prognosis subtype of gastric cancer characterized by the miR-200 family" @default.
- W1981927724 doi "https://doi.org/10.1158/1538-7445.am2014-1474" @default.
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