Mutually distinguishing microRNA signatures of breast, ovarian and endometrial cancers in vitro

Hirschfeld,Marc; Ge,Isabel; Rücker,Gerta; Waldschmidt,Julia; Mayer,Sebastian; Jäger,Markus; Voigt,Matthias; Kammerer,Bernd; Nöthling,Claudia; Berner,Kai; Weiss,Daniela; Asberger,Jasmin; Erbes,Thalia

doi:10.3892/mmr.2020.11466

Mutually distinguishing microRNA signatures of breast, ovarian and endometrial cancers in vitro

Authors:
- Marc Hirschfeld
- Isabel Ge
- Gerta Rücker
- Julia Waldschmidt
- Sebastian Mayer
- Markus Jäger
- Matthias Voigt
- Bernd Kammerer
- Claudia Nöthling
- Kai Berner
- Daniela Weiss
- Jasmin Asberger
- Thalia Erbes
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Affiliations: Department of Gynecology and Obstetrics, Faculty of Medicine and Medical Center, University of Freiburg, D‑79106 Freiburg, Germany, Institute of Medical Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, D‑79104 Freiburg, Germany, Praxis of Plastic and Aesthetic Surgery and Evangelian Deaconry Hospital, D‑79110 Freiburg, Germany, Center for Biological Systems Analysis, University of Freiburg, D‑79104 Freiburg, Germany
Published online on: August 27, 2020 https://doi.org/10.3892/mmr.2020.11466
Pages: 4048-4060

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Abstract

Early diagnosis and therapy in the first stages of a malignant disease is the most crucial factor for successful cancer treatment and recovery. Currently, there is a high demand for novel diagnostic tools that indicate neoplasms in the first or pre‑malignant stages. MicroRNAs (miRNA or miR) are small non‑coding RNAs that may act as oncogenes and downregulate tumor‑suppressor genes. The detection and mutual discrimination of the three common female malignant neoplasia types breast (BC), ovarian (OC) and endometrial cancer (EC) could be enabled by identification of tumor entity‑specific miRNA expression differences. In the present study, the relative expression levels of 25 BC, EC and OC‑related miRNAs were assessed by reverse transcription‑quantitative PCR and determined using the 2‑ΔΔCq method for normalization against the mean of four housekeeping genes. Expression levels of all miRNAs were analyzed by regression against cell line as a factor. An expression level‑based discrimination between BC and OC cell types was obtained for a subgroup of ten different miRNA types. miR‑30 family genes, as well as three other miRNAs, were found to be uniformly upregulated in OC cells compared with BC cells. BC and EC cells could be distinguished by the expression profiles of six specific miRNAs. In addition, four miRNAs were differentially expressed between EC and OC cells. In conclusion, miRNAs were identified as a potential novel tool to detect and mutually discriminate between BC, OC and EC. Based on a subset of 25 clinically relevant human miRNA types, the present study could significantly discriminate between these three female cancer types by means of their expression levels. For further verification and validation of miRNA‑based biomarker expression signatures that enable valuable tumor detection and characterization in routine screening or potential therapy monitoring, additional and extended in vitro analyses, followed by translational studies utilizing patients' tissue and liquid biopsy materials, are required.

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