Abstract 1961: Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Background: Gastric cancer is composed of disease subgroups with heterogeneous clinical and biological behaviors. A previous study identified two subgroups with distinct gene-expression profiles strongly associated with prognosis. To identify molecular biologic differences between these two subgroups, we performed an integrative analysis of mRNA, microRNA, and protein expression. Methods: Array technologies were used to generate microRNA and protein expression profiles of frozen tissue samples from 60 patients with gastric cancer. All patients underwent curative gastric resection in 2005 and distributed from stage I to IV and their clinical characteristics were collected. BRB-ArrayTools were used for microarray data analysis. Data was compared between gastric cancer tissue and normal gastric tissue and also between two different prognostic groups. Aberrantly expressed microRNA and associated mRNA in patients with poor-prognosis gastric cancer were validated by quantitative RT-PCR and tissue microarray, respectively. Results: Four microRNAs were aberrantly expressed in gastric cancer tissue, especially poor prognostic group (P < 0.05). In the poor-prognosis subgroup, miR-196b showed the most significantly high expression patterns and also miR-135b, miR-93. On the contrary, miR-29c* was down-regulated. MiR-196b expression was positively correlated with HOXA10 expression (r = 0.726; P < 0.001), which was significantly increased in poor-prognosis patients (P < 0.001). HOXA10 protein-positive expression was identified in 56 of 368 gastric cancer tissue microarray samples. In reverse-phase protein array, 46/124 proteins were expressed differently (P < 0.05); COX2 (P < 0.001) and cyclin B1 (P = 0.017) were clearly over-expressed in the poor-prognosis group. Conclusion: Integrative analysis of RNA and protein expression profile facilitates interpretation of the molecular biologic heterogeneity of cancer. Co-activation of miR-196b and HOXA10 characterized a poor-prognosis subgroup of patients with gastric cancer. As HOXA10 is involved in the proliferation of hematopoietic stem cells and progenitor cells, the relevance of hematopoietic progenitor cell and gastric cancer development/progression should be further investigated. Citation Format: Jae Yun Lim, Sun Och Yoon, So-Young Seol, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Ju-Seog Lee, Jae Yong Cho. Overexpression of miR-196b and HOXA10 characterize a poor-prognosis gastric cancer subtype. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1961. doi:10.1158/1538-7445.AM2013-1961