Discovery of potential serum and urine-based microRNA as minimally-invasive biomarkers for breast and gynecological cancer

Article type: Research Article

Authors: Ritter, Andrea^{a; b} | Hirschfeld, Marc^{a; b; c} | Berner, Kai^{a; b} | Jaeger, Markus^{a; b} | Grundner-Culemann, Franziska^d | Schlosser, Pascal^d | Asberger, Jasmin^{a; b} | Weiss, Daniela^{a; b} | Noethling, Claudia^{a; b} | Mayer, Sebastian^e | Erbes, Thalia^{a; b; *}

Affiliations: [a] Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, Germany | [b] Faculty of Medicine, University of Freiburg, Freiburg, Germany | [c] Institute of Veterinary Medicine, Georg-August-University Goettingen, Goettingen, Germany | [d] Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany | [e] Department of Gynecology and Obstetrics, Hospital Memmingen, Memmingen, Germany

Correspondence: [*] Corresponding author: Thalia Erbes, Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, Germany. E-mail: [email protected].

Abstract: BACKGROUND: Deregulated microRNAs (miRNAs) in breast and gynecological cancer might contribute to improve early detection of female malignancies. OBJECTIVE: Specification of miRNA types in serum and urine as minimally-invasive biomarkers for breast (BC), endometrial (EC) and ovarian cancer (OC). METHODS: In a discovery phase, serum and urine samples from 17 BC, five EC and five OC patients vs. ten healthy controls (CTRL) were analyzed with Agilent human miRNA microarray chip. Selected miRNA types were further investigated by RT-qPCR in serum (31 BC, 13 EC, 15 OC patients, 32 CTRL) and urine (25 BC, 10 EC, 10 OC patients, 30 CTRL) applying two-sample t-tests. RESULTS: Several miRNA biomarker candidates exhibited diagnostic features due to distinctive expression levels (serum: 26; urine: 22). Among these, miR-518b, -4719 and -6757-3p were found specifically deregulated in BC serum. Four, non-entity-specific, novel biomarker candidates with unknown functional roles were identified in urine (miR-3973; -4426; -5089-5p and -6841). RT-qPCR identified miR-484/-23a (all p⩽ 0.001) in serum as potential diagnostic markers for EC and OC while miR-23a may also serve as an endogenous control in BC diagnosis. CONCLUSIONS: Promising miRNAs as liquid biopsy-based tools in the detection of BC, EC and OC qualified for external validation in larger cohorts.

Keywords: miR-484, miR-23a-3p, liquid biopsy, miRNA, endometrial cancer, ovarian cancer, breast cancer, screening

DOI: 10.3233/CBM-190575

Journal: Cancer Biomarkers, vol. 27, no. 2, pp. 225-242, 2020