Abstract 1966: Analysis of micro RNAs in the racial disparity of endometrial cancer .

Abstract

Abstract In the United States endometrial cancer is recognized for having a distinct racial disparity. This disparity by race occurs for both the prevalence of disease and for survival outcome. Caucasians are about two times more likely to develop endometrial cancer than are African Americans. However, African American women are more likely to die from this disease than are Caucasians. The basis for this disparity remains unknown. Previous studies have identified differences in the types and frequencies of gene mutations among endometrial cancers from Caucasians and African-Americans suggesting that the tumors from these two groups might have differing underlying genetic defects. In addition previous studies have utilized gene expression microarray studies in an effort to identify differentially expressed transcripts between African-American and Caucasian women's endometrial cancers. MicroRNAs (miRNA) have emerged as additional regulators of cell function and their aberrant expression and function is noted in many diseases including endometrial cancers. We performed an analysis in a set of early stage endometrial cancers to identify whether differences in miRNA expression may underlie some biologic aspect of this racial disparity. We assayed 50 laser microdissected endometrial cancers using TaqMan Low Density arrays and compared the expression of miRNAs between African-American (9 patients) and Caucasian (41 patients) cancers. Similarly to previous mRNA comparisons by our group, no global differences in miRNA expression were evident between African American and Caucasian endometrial cancers. We further refined our analyses using Partial Least Squares Regression (PLSR) where race-, stage-, and grade-dependent variances were examined which indicated that the depth of invasion affects global associations. An analysis of variance (ANOVA) that considered race and stage as factors and a Wilcoxon signed rank test of these groups revealed a small number of differentially expressed miRNAs. Since the unbalanced sample sizes (41 Caucasian versus 9 African-American cases) may introduce bias, we performed a paired analysis (9 AA cancers v. 9 C cancers). Of several differentially identified miRNAs, hsa-miR-337-3p was consistently identified in class comparisons. We validated the differential expression of hsa-miR-337-3p in an independent set of endometrial cancers from African Americans (n=24) and Caucasians (n=23). Analysis of normal endometrial epithelial expression indicated that hsa-miR-337-3p expression is down-regulated in cancers as compared to normal expression and that there is no difference in expression of hsa-miR-337-3p in the normal endometrium according to race. These data indicate that hsa-mir-337-3p is specifically down-regulated in Caucasian women's endometrial cancers and may play a role in the more frequent development of uterine cancers in Caucasians. Citation Format: G. Larry Maxwell, GVR Chandramouli, Tracy Litzi, Andrew Berchuck, Thomas P. Conrads, John I. Risinger. Analysis of micro RNAs in the racial disparity of endometrial cancer . [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 1966. doi:10.1158/1538-7445.AM2013-1966