MiR-371a-3p Serum Levels Are Increased in Recurrence of Testicular Germ Cell Tumor Patients.

Angelika Terbuch,Florian Posch,Anna Lembeck,Maximilian Seles,Jan Adiprasito,Karl Pummer,Christiane Klec,Michael Stotz,Margit Resel,Martin Pichler,Herbert Stöger,Georg Hutterer,Joanna Szkandera,Georg Pichler,Verena Stiegelbauer,Thomas Bauernhofer,Armin Gerger

doi:10.3390/ijms19103130

Abstract

Metastatic testicular germ cell tumors (TGCTs) are a potentially curable disease by administration of risk-adapted cytotoxic chemotherapy. Nevertheless, a disease-relapse after curative chemotherapy needs more intensive salvage chemotherapy and significantly worsens the prognosis of TGCT patients. Circulating tumor markers (β-subunit of human chorionic gonadotropin (β-HCG), alpha-Fetoprotein (AFP), and Lactate Dehydrogenase (LDH)) are frequently used for monitoring disease recurrence in TGCT patients, though they lack diagnostic sensitivity and specificity. Increasing evidence suggests that serum levels of stem cell-associated microRNAs (miR-371a-3p and miR-302/367 cluster) are outperforming the traditional tumor markers in terms of sensitivity to detect newly diagnosed TGCT patients. The aim of this study was to investigate whether these miRNAs are also informative in detection of disease recurrence in TGCT patients after curative first line therapy. For this purpose, we measured the serum levels of miR-371a-3p and miR-367 in 52 samples of ten TGCT patients at different time points during disease relapse and during salvage chemotherapy. In our study, miR-371a-3p levels in serum samples with proven disease recurrence were 13.65 fold higher than levels from the same patients without evidence of disease (p = 0.014). In contrast, miR-367 levels were not different in these patient groups (p = 0.985). In conclusion, miR-371a-3p is a sensitive and potentially novel biomarker for detecting disease relapse in TGCT patients. This promising biomarker should be investigated in further large prospective trials.

Highlights

Testicular germ cell tumors (TGCTs) represent the most common malignancy among men aged between 20 and 40 years [1]
TGCTs are sub-classified according to their underlying histology into seminomatous (SGCT) and non-seminomatous germ cell tumors (NSGCT), which are distinct in terms of biology, prognosis, and treatment strategy
In metastatic TGCTs, prognosis and therapy depend on the size and location of metastases, as well as levels of circulating tumor markers

Summary

Introduction

Testicular germ cell tumors (TGCTs) represent the most common malignancy among men aged between 20 and 40 years [1]. For follow-up monitoring to detect disease relapse, blood-based tumor markers alpha-Fetoprotein (AFP), the β-subunit of human chorionic gonadotropin (β-HCG), and Lactate Dehydrogenase (LDH) are commonly measured [3]. In a prospectively conducted biomarker study, Dieckmann et al clearly demonstrated that miR-371a-3p has the best discriminative power with 88.7% sensitivity and 93.4% specificity, outperforming AFP, β-HCG, and LDH which showed a combined 50% sensitivity [19]. Despite this encouraging data in the setting of detection of primary TGCTs and disease monitoring, very little information about the value of these miRNAs in TGCT disease-recurrence is published.

Results

Discussion

Materials and Methods