Circulating microRNAs as potential diagnostic biomarkers in ovarian cancer

Abstract: Background: Ovarian cancer is the seventh most frequent form of malignant diseases in women worldwide. Over 150.000 women die from it every year, placing it as the most lethal malignant gynecological disease in terms of mortality. More than 70 percent of all ovarian cancer patients are diagnosed at a late stage disease with poor prognosis. In early stages, the five-year survival rates are around 90 percent, necessitating the need for screening biomarkers. MicroRNAs displayed promising potential as early diagnostics in various malignant diseases including ovarian cancer. The presented study aimed at identifying single microRNAs and microRNA combinations detecting ovarian cancer in vitro and in vivo. Methods: Intracellular, extracellular and urinary microRNA expression levels of twelve microRNAs (let-7a, let-7d, miR-10a, miR-15a, miR-15b, miR-19b, miR-20a, miR-21, miR-100, miR-125b, miR-155, miR-222) were quantified performing quantitative realtime-PCR. Therefore, the three ovarian cancer cell lines SK-OV-3, OAW-42, EFO-27 as well as urine samples of ovarian cancer patients and healthy controls were analyzed. Results: All 12 analyzed microRNAs could be detected in vitro and in vivo. Hypoxia and acidosis showed significant effects on the single miRNA expression levels in a paired two-tailed t-test. MiR-15a, miR-20a and miR-222 showed significant expression level alterations extracellulary whereas miR-125b did intracellularly across all three cell lines. MicroRNA expression alterations in single cell lines suggest subtype specificity in both compartments. Furthermore, the study demonstrates the feasibility to detect the 12 miRNAs in urine samples. MiR-15a was significantly upregulated whereas let-7a was significantly down-regulated in ovarian cancer patients. Conclusion: Cell culture media analyses prove that microRNAs are secreted from cells into their surroundings which emphasizes their potential as biomarkers in liquid biopsies. The feasibility to detect an upregulation of miR-15a and a downregulation of let-7a in vivo enables to distinguish urine of ovarian cancer patients from healthy controls. Resulting, the analyzed miRNAs qualify for possible circulating biomarkers in liquid biopsies of ovarian cancer patients. Hypoxia and acidosis driven microRNA alterations might indicate early tumorigenesis

Sprache
Englisch
Umfang
Online-Ressource
Anmerkungen
Universität Freiburg, Dissertation, 2019
Standort
Deutsche Nationalbibliothek Frankfurt am Main

Schlagwort
Cancer
Biochemical markers

Urheber
Beteiligte Personen und Organisationen
Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2020

DOI
10.6094/UNIFR/166490
URN
urn:nbn:de:bsz:25-freidok-1664901
Rechteinformation
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Letzte Aktualisierung
25.03.2025, 13:48 MEZ

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Beteiligte

Entstanden

  • 2020

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