miR-371a-3p, miR-373-3p and miR-367-3p as Serum Biomarkers in Metastatic Testicular Germ Cell Cancers Before, During and After Chemotherapy

Cells. 2019 Oct 8;8(10):1221. doi: 10.3390/cells8101221.

Abstract

Background: LDH (lactate dehydrogenase), AFP (alpha-fetoprotein) and β-HCG (human chorionic gonadotropin) are used in diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. Our aim was to investigate the association between levels of miR-371a-3p, miR-373-3p and miR-367-3p and clinical features in metastatic TGCC.

Methods: relative levels of miR-371a-3p, miR-373-3p and miR-367-3p were evaluated in serum of metastatic TGCC patients. A prospectively included and a retrospectively selected cohort were studied (total patient number = 109). Blood samples were drawn at start of chemotherapy and during follow-up. Serum microRNA (miR) levels were determined using the ampTSmiR test.

Results: at start of chemotherapy, miR-371a-3p, miR-373-3p and miR-367-3p levels were positively correlated to LDH. The median level of these miRs was higher in patients who developed a relapse after complete biochemical remission (n = 34) than in those who had complete durable remission (n = 60). Higher levels of miR-367-3p were found in patients with refractory disease (n = 15) compared to those who had complete response. miR levels decreased during the first week of chemotherapy in patients with complete response and stayed below threshold after one year of treatment.

Conclusion: high miR levels at start of chemotherapy are associated with worse clinical outcome and can assist in early diagnosing of relapses.

Keywords: AFP; LDH; microRNA; serum biomarkers; testicular germ cell cancer; β-HCG.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / blood
  • Bleomycin / therapeutic use
  • Chorionic Gonadotropin / blood
  • Cisplatin / therapeutic use
  • Cohort Studies
  • Etoposide / therapeutic use
  • Humans
  • L-Lactate Dehydrogenase / blood
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Neoplasms, Germ Cell and Embryonal / blood*
  • Neoplasms, Germ Cell and Embryonal / drug therapy
  • Testicular Neoplasms / blood*
  • Testicular Neoplasms / drug therapy
  • Young Adult
  • alpha-Fetoproteins / analysis

Substances

  • AFP protein, human
  • Biomarkers, Tumor
  • Chorionic Gonadotropin
  • MIRN367 microRNA, human
  • MIRN371 microRNA, human
  • MIRN373 microRNA, human
  • MicroRNAs
  • alpha-Fetoproteins
  • Bleomycin
  • Etoposide
  • L-Lactate Dehydrogenase
  • Cisplatin

Supplementary concepts

  • Testicular Germ Cell Tumor