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

Ximena Rosas Plaza,Jourik A Gietema,Leendert H J Looijenga,Marcel A T M Van Vugt,Ton Van Agthoven,Coby Meijer,Steven De Jong

doi:10.3390/cells8101221

Ximena Rosas Plaza, Jourik A Gietema + Show 5 more

Open Access

https://doi.org/10.3390/cells8101221

Copy DOI

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.

Highlights

Testicular germ cell cancer (TGCC) is rare, but the most common malignancy among youngCaucasian men
This study indicates that serum levels of members of the miR-371 cluster and miR-367-3p before start of chemotherapy correlate with various clinical features in metastatic testicular germ cell cancer (TGCC) patients, including disease burden
TGCC patients belonging to the good international germ cell cancer collaborative group (IGCCCG) prognosis group showed lower median miR levels compared to the intermediate and poor risk groups

Summary

Introduction

Testicular germ cell cancer (TGCC) is rare, but the most common malignancy among youngCaucasian men. The tumor markers LDH (lactate dehydrogenase), AFP (alpha-fetoprotein) and β-HCG (human chorionic gonadotropin) produced by some of the cancer cells and measurable in serum contribute to establish the diagnosis, with LDH being the less specific marker. These markers are used for risk stratification and follow-up of patients with metastatic disease, making them a highly valuable tool for oncologists in daily practice. 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). Methods: relative levels of miR-371a-3p, miR-373-3p and miR-367-3p were evaluated in serum of metastatic TGCC patients.

Objectives

Methods

Results

Conclusion