Systemic miRNA-195 Differentiates Breast Cancer from Other Malignancies and Is a Potential Biomarker for Detecting Noninvasive and Early Stage Disease

Abstract

Abstract Learning Objectives After completing this course, the reader will be able to: Describe the site-specific dysregulation of some miRNAs and explain their potential as non-invasive biomarkers for diagnosis, prognostication, or markers of treatment response.Cite the characteristics reflected by circulating miR-195 and explain how elevated levels could be used as a breast tumor marker. CME This article is available for continuing medical education credit at CME.TheOncologist.com Purpose. The potential of microRNAs (miRNAs) as novel tumor markers has been the focus of recent scrutiny because of their tissue specificity, stability, and association with clinicopathological parameters. Data have emerged documenting altered systemic miRNA expression across a spectrum of cancers; however, it remains uncertain as to whether circulating miRNAs are tumor specific. Our aim was to assess a panel of cancer-associated miRNAs in the circulation of patients with various malignancies, to determine whether these “oncomirs” were tumor specific, and thus to establish whether systemic miRNA analysis has utility in cancer diagnosis. Patients and Methods. Whole blood samples were prospectively collected from preoperative cancer patients (breast, prostate, colon, and renal cancer and melanoma; n = 163) and healthy age- and sex-matched controls (n = 63). Total RNA was isolated, and a panel of seven miRNAs was quantified by real-time quantitative polymerase chain reaction in each sample. Results. Differential expression of the general oncomirs let 7a, miR-10b, and miR-155, was observed in the majority of cancer patients in a nonspecific manner. Significantly, elevated circulating miR-195 was found to be breast cancer specific and could differentiate breast cancer from other cancers and from controls with a sensitivity of 88% at a specificity of 91%. A combination of three circulating miRNAs, including miR-195, further enhanced the discriminative power of this test for breast cancer to 94%. Conclusion. These findings suggest that individual cancers display specific systemic miRNA profiles, which could aid in discriminating among cancer types. This finding is of notable clinical consequence because it illustrates the potential of systemic miRNAs as sensitive, specific, noninvasive cancer biomarkers.