Abstract 3156: MicroRNA let-7a is a possible new marker for predicting the effect of paclitaxel in epithelial ovarian cancer
Authors: Lu Lingeng , Schwartz Peter , Scarampi Luca , Canuto Emilie M. , Rutherford Thomas , Katsaros Dionyssios , Yu Herbert 
Published: June 2012

Abstract
MicroRNA let-7 is a family of small non-coding RNAs post-transcriptionally regulating the expression of genes that are involved in cell proliferation, apoptosis and therapy response. Let-7 is shown in vitro to affect the sensitivity of cancer cells to platinum. Let-7a, a member of the let-7 family, is also found to induce ovarian cancer cell resistance to paclitaxel (taxol). The purpose of this study is to investigate the relationship of let-7a expression and survival outcomes of epithelial ovarian cancer patients treated with different chemotherapy. Levels of let-7a and RNU48 (an endogenous control for normalization) were analyzed using the Taqman® microRNA assays in 178 primary epithelial ovarian cancer patients who received chemotherapy after debulking surgery. Survival analysis was performed to assess the associations of let-7a expression with disease outcomes and chemotherapy. Patients with poor response to platinum with taxol had significantly higher let-7a expression than those with complete response, while no difference in let-7a expression between responders and non-responders treated with platinum without taxol. We also found that in patients treated with platinum without taxol, high let-7a was associated with better survival. The Hazard Ratios (HRs) for death were 0.55 (95% CI: 0.29-1.05) and 0.52 (95% CI: 0.29-0.96) when comparing patients with medium or high let-7a to those with low let-7a, respectively (p for trend = 0.033). Similar HRs for disease progression were 0.49 (95% CI: 0.27-0.91) and 0.48 (0.26-0.89), respectively (p for trend = 0.020). These associations became less significant when patient age at surgery, disease stage, tumor grade and histological type were adjusted in the analysis. However, in patients treated with platinum and taxol, high let-7a expression was associated with poor survival. The HRs for death were 1.70 (95% CI: 0.50-5.81) for medium and 3.87 (95% CI: 1.28-11.66) for high let-7a (p for trend = 0.009). The HRs for disease progression were 2.85 (95% CI: 0.99-8.22) for medium and 3.48 (95% CI: 1.25-9.67) for high let-7a (p for trend = 0.016). These associations remained significant after the analyses were adjusted for patient age at surgery, disease stage, tumor grade and histological type. These results suggest that let-7a may play different roles in disease outcome when patients received different combinations of chemotherapy, and the microRNA may serve as a marker for selecting patient who will respond to taxol treatment. This finding may have significant implication in the treatment of epithelial ovarian cancer with regard to reducing treatment cost and minimizing drug toxicity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3156. doi:10.1158/1538-7445.AM2011-3156