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

Cancer Biomark. 2020;27(2):225-242. doi: 10.3233/CBM-190575.

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

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / urine
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / urine
  • Case-Control Studies
  • Endometrial Neoplasms / blood
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / urine
  • Female
  • Humans
  • Liquid Biopsy / methods
  • Middle Aged
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / urine
  • Prognosis

Substances

  • Biomarkers, Tumor