Abstract 3157: Clinical relevance of miR-200 family members in various cancers
Authors: Pecot Chad V. , Akbani Rehan , Ivan Cristina , Unruh Anna K. , Wu Sherry , Rupaimoole Rajesh , Bottsford-Miller Justin , Zand Behrouz , Tucker Susan L. , Coleman Robert L. , Baggerly Keith A. , Sood Anil K. 
Published: August 2012

Abstract
Introduction: Low expression of miR-200 family members in some cancers has been linked to epithelial-mesenchymal transition and subsequent metastatic spread. Thus, low expression of miR-200 members would be expected to reduce survival. We investigated whether expression levels of miR-200 family members are associated with clinical outcome in several cancer types. Methods: We used clinically annotated data from The Cancer Genome Atlas (TCGA). Our preliminary analysis focused on nine different cancer types, subsequently reduced to four that had a large number of samples (&gt;200). Expression data for all five miR-200 members (miR-141, -200a, -200b, -200c, and -429) were obtained from either Agilent miRNA microarrays (8x15K; glioblastoma multiforme and ovarian cancers) or miR-Seq (Illumina GA and HiSeq; breast and clear cell renal cancers). Approximately 2/3 of the samples for each tumor type were used as a training cohort to obtain the miRNA expression thresholds yielding the most significant log rank test p-values (one-tailed test), thus dividing the data into good and poor prognosis groups. These thresholds were then used to divide the data in the remaining 1/3 of the samples that functioned as independent validation cohorts, and p-values were computed for those cohorts. The same procedure was repeated again to look for significant differences in progression free survival. Kaplan-Meier curves were also plotted for all datasets, with a p-value &lt; 0.05 considered significant. Results: Amongst the cancer types assessed, for ovarian (n=579) and renal cancers (n=474), low expression of a miR-200 family member was significantly associated with worse overall survival. In the ovarian cancer validation set (209 samples), median overall survival was 1150 versus 1700 days for low versus high miR-200c expression, respectively (p=0.019). In the renal cancer validation set (168 samples), median overall survival was 1900 versus &gt;3500 days for low versus high miR-200a expression, respectively (p=0.005). However, in breast cancer (n=325) and glioblastoma multiforme (GBM, n=487), low expression of a miR-200 member was associated with an improved clinical outcome. In the breast cancer validation set (113 samples), median overall survival was &gt; 7000 versus 3100 days for low versus high miR-141 expression, respectively (p=0.036). In the GBM validation set (174 samples), median progression free survival was 290 versus 150 days for low versus high miR-429 expression, respectively (p=0.009). Discussion: Here we show that altered expression levels of miR-200 members may have clinical relevance in common cancers. Interestingly, depending on the cancer type, low miR-200 member levels may either portend a better or worse prognosis. This study highlights the need to further elucidate novel mechanisms of the miR-200 family and perhaps exploit their diverse functions for therapeutic intent.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3157. doi:1538-7445.AM2012-3157