Abstract
Abstract BACKGROUND: Various staging and grading systems are used to classify the gastrointestinal neuroendocrine tumors (GNTs). These systems attempt to stratify tumors, in order to predict survival after resection and the rate of progression to metastatic disease. At present, no specific molecular markers are available for diagnosis, prognosis or therapeutic targeting of GNTs. Microarray profiling analysis for the expression of miRNAs was performed on GNTs of stomach, small intestine, appendix, colon and rectum. MATERIALS AND METHODS: Database search was carried out for patients with GNTs and pathological staging was performed in accordance with AJCC Cancer Staging manual (7th ed). The tumors evaluated included stomach (Stage I & II: 8 cases, Stage III&IV: 3 cases) , Ileum and cecum (Stage I and II:5, Stage III& IV: 17), appendix (Stage I &II: 3, goblet cell carcinoid: 7), and rectum (Stage I and II: 15, Stage III and IV: 3 cases). Kaplan Meir analysis revealed a worse overall survival of Stage III and IV tumors in comparison to Stage I and II in all subgroups. Formalin Fixed Paraffin Embedded (FFPE) archival tissue was obtained. Total RNA was isolated from FFPE tissue using the RNeasy Kit (Qiagen, Valencia, CA, USA). RNA was quantified and its purity was evaluated by the absorption ratio at 260/280nm using NanoDrop 2000 (Thermo Scientific, Pittsburgh, PA, USA). The microRNA profiling was performed by LC Sciences (Houston, TX) using miRBase v20 and data was normalized using selective housekeeping miRNAs. RESULTS: The most significantly altered miRNAs amongst various groups are tabulated (Table no.1) CONCLUSION: Stage III and IV GNTs are biologically distinct in comparison to Stage I and II GNTs. There is a significant up-regulation or down-regulation of specific miRNAs in these tumors. Bioinformatics analysis and further validation by RT-PCR are being performed which will likely provide information on the role of specific genes regulated by these miRNAs in GNTs. Table no.1: Differential expression of miRNAs in GNTsmiRNAIleum Stage III and IV (G1)Ileum Stage I and II (G2)log G2/G1miR-9-5p(Tumor suppressor gene, TSG)621005-4.02miR-424-5p(TSG)4962853-2.52miR-376c-3p (Tumor oncogene, TO)553862.68miR-301a-3p (TO)7951252.66miRNAStomach Stage III and IV (G1)Stomach Stage I and II (G2)log G2/G1miR-18a-5p (TSG)2843635.39miR-19a-3p (TSG)2864795.17miR-6722-5p (TO)1211278-3.4miR-6858-3p (TO)112820-2.87miRNARectum Stage III and IV (G1)Rectum stage I and II (G2)log G2/G1miR-34a-5p (TSG)216933-2.11miR-150-5p (TSG)3981440-1.85miR-122-5p (TO)17131024.07miR-653-3p (TO)16272142.93miRNAGoblet cell carcinoid Stage III and IV (G1)Appendiceal carcinoid Stage I and II (G2)log G2/G1miR-642a-5p (TSG)11180-17.49miR-642b-5p (TSG)9620-17.28miR-7843-5p (TO)9916944.09miR-6775-5p (TO)134043601.70 Citation Format: Amarpreet Bhalla, Shadan Ali, Fazlul Sarkar, Anthony Shields, Amy Jencks, Romil Nathan, Vinod B. Shidham. Differential expression of microRNAs in gastrointestinal neuroendocrine tumors. [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 3552. doi:10.1158/1538-7445.AM2014-3552
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