Screening For Plasma Micro Rnas As Biomarkers For Breast Cancer Detection

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Introduction: MicroRNAs (miRNAs) are small, non-coding RNA molecules that play critical roles in a variety of physiological and pathological processes, including carcinogenesis of breast cancer. The research regarding miRNA discovery and characterization is emerging and there is consensus in the literature that miRNAs are excellent candidate biomarkers for human cancer. Cancer specific miRNAs have been detected in tumors as well as in serum, plasma, and other body fluids. However, no extensive profiling of circulating miRNAs in breast cancer patients has been done to date, although several studies investigated a limited number of miRNA panels. Methods: We investigated the miRNA profile in plasma samples collected before surgery from 10 pathologically confirmed breast cancer patients, one month after surgery from 2 breast cancer patients, and from 10 healthy women controls that were frequency matched to cases on age and race. RNA was extracted from plasma using the mirVana Paris RNA isolation kit (Ambion) and miRNA profiling was done using the TaqMan® Human MicroRNA Array Set v.2.0 (Applied Biosystems), enabling the detection of 667 human mature miRNAs. Plasma miRNA levels were calculated using the well established comparative Ct method (ΔΔCt) relative to the selected controls, and both Wilcoxon rank-sum tests and t tests were used to compare plasma miRNA levels between control subjects and cancer patients. Correlation between miRNAs was assessed separately in cancer and control subjects. Results: Ten miRNAs (1.5% of total) were detected in plasma of all subjects and 12 miRNAs (1.8% of total) were detected in at least 80% of cases and controls, respectively. Of these, 17 miRNAs presented a significant differential expression in plasma between cases and controls (p<0.05). Only one of these (has-miR-191) was previously described as being differentially expressed in breast cancer tissue compared to normal breast tissue. Based on their ability to discriminate between cancer and controls, their fold change, p values, correlation coefficients and post-surgical levels, we selected 6 candidate miRNAs that will be validated in a larger sample set of 50 cases and 50 controls. The p values of these six candidates ranged between <0.0001 and 0.005 and the fold change between cases and controls ranged from 33.85 to 111.80. Conclusion: We identified several circulating miRNAs that are differentially expressed between breast cancer patients and normal controls, and therefore could serve as biomarkers for breast cancer detection if confirmed by future studies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3031.