Abstract 4672: MicroRNA expression signature of gastric carcinoma patients treated with neoadjuvant chemotherapy

Abstract

Abstract Background: Gastric cancer (GC) is a common malignancy that is a leading cause of cancer mortality worldwide. The curative treatment of GC requires gastric ressection. However, most patients are not cured by only surgery treatment. Recently, various chemotherapy schemes have been used in the neoadjuvant or adjuvant treatment scenario. The underlying principles behind neoadjuvant therapy are to improve ressectability of the tumor by tumor shrinkage/downstaging and to treat occult metastatic disease as early as possible. A major challenge for improving clinical outcomes is to understand the molecular mechanisms that may play essential roles in tumorigenesis. miRNAs have been shown to have prognostic and diagnostic value in certain types of cancer. The expression levels of several microRNAs (miRNAs) have been found to be correlated with GC prognosis and could determine the clinical response for neoadjuvant chemotherapy in some patients. Objective: To identify microRNAs differentially expressed in the group of GC patients treated by neoadjuvant chemotherapy compared with normal gastric tissue. Methods: We selected 53 GCs from a retrospective database of patients treated at A C Camargo Cancer Center. All the patients had received ECF, DCF or ECX chemotherapy prior the surgery subsequently undergoing a complete (R0) resection. The entire tumor beds of the specimens were histologically evaluated. The total RNA was extracted from paraffin-embedded tissues of 53 biopsies collected prior the treatment, as well as, from 18 normal gastric tissue. We determined the expression of 377 miRNA by real-time PCR and calculated using the 2_ΔΔCt method. Results: We have identified 14 differential miRNAs expression. We detected 9 up-regulated miRNAs: hsa-miR-135b-4395372 (88,7%), hsa-miR-15b-4373122 (88,7%), hsa-miR-215-4373084 (81,1%), hsa-miR-224-4395210 (81,1%), hsa-miR-23b-4373073 (83,0%), hsa-miR-27a-4373287 (92,5%), hsa-miR-331-3p-4373046 (98,1%), hsa-miR-374a-4373028 (92,5%), hsa-miR-374b-4381045 (83,0%) and 5 down-regulated miRNAs: hsa-miR-148a-4373130 (83,0%), hsa-miR-26a-4395166 (86,8%), hsa-miR-26b-4395167 (84,9%), hsa-miR-429-4373203 (84,9%), hsa-miR-522-4395524 (86,8%). Conclusions: We showed over-expressed and down-expressed miRNAs in GC treated with neoadjuvant chemotherapy compared with normal gastric tissue. This is a preliminary result; however, the association between our data and clinicopathological findings in this group of patients should be able to determine a predictable miRNA signature. Citation Format: Michelle M. Barcelos Baldoni, Cláudia M. Coutinho Camillo, Maria Dirlei F. Begnami. MicroRNA expression signature of gastric carcinoma patients treated with neoadjuvant chemotherapy. [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 4672. doi:10.1158/1538-7445.AM2014-4672