Clinical utility of plasma miR-371a-3p in germ cell tumors

J Cell Mol Med. 2019 Feb;23(2):1128-1136. doi: 10.1111/jcmm.14013. Epub 2018 Dec 7.

Abstract

Germ cell tumours predominantly of the testis ((T)GCTs) are remarkably chemotherapy sensitive. However, a small proportion of patients fail to be cured with cisplatin-based combination chemotherapy. miR-371a-3p is a new liquid biopsy biomarker for (T)GCTs. The aim of this study was to evaluate clinical utility of plasma miR-371a-3p level in patients starting systemic chemotherapy. Patients were included before the first cycle (N = 180) and second cycle (N = 101) of systemic first line chemotherapy, treated between July 2010 and May 2017. Plasma miR-371a-3p levels were measured with the ampTSmiR test and compared to disease characteristics and outcome. Pretreatment plasma miR-371a-3p levels were increased in 51.7% of cases and associated with number of metastatic sites, presence of lung, retroperitoneal, and mediastinal lymph node metastases, S - stage, IGCCCG risk group, and response to therapy. Patients with a negative pretreatment plasma level had better progression-free survival (PFS) and overall survival (OS) compared to patients being positive for miR-371a-3p (hazard ratio [HR] = 0.26, 95% confidence interval [CI] 0.09-0.71, P = 0.02 for PFS and HR = 0.21, 95% CI 0.07-0.67, P = 0.03 for OS, respectively). Patients negative for miR-371a-3p in both samples had a superior PFS (HR = 0.10, 95% CI 0.01-21.49, P = 0.02) and OS (HR = 0.08, 95% CI 0.01-27.81, P = 0.008) compared to patients with miR-371a-3p positive in both samples (multivariate analyses were non-significant). In total 68% of the patients were S0. This study demonstrates clinical value of plasma miR-371a-3p level in chemotherapy naïve (T)GCT patients starting first line of chemotherapy to predict prognosis.

Keywords: (testicular) germ cell tumours; miR-371a-3p; prognostic liquid biopsy biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Cisplatin / therapeutic use
  • Female
  • Humans
  • Lymphatic Metastasis / drug therapy
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Neoplasms, Germ Cell and Embryonal / blood*
  • Neoplasms, Germ Cell and Embryonal / drug therapy
  • Neoplasms, Germ Cell and Embryonal / genetics*
  • Neoplasms, Germ Cell and Embryonal / pathology
  • Prognosis
  • Progression-Free Survival
  • Retrospective Studies
  • Testicular Neoplasms / blood*
  • Testicular Neoplasms / drug therapy
  • Testicular Neoplasms / genetics*
  • Testicular Neoplasms / pathology
  • Testis / drug effects
  • Testis / pathology
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MIRN371 microRNA, human
  • MicroRNAs
  • Cisplatin