The metastatic potential of seminomatous germ cell tumours is associated with a specific microRNA pattern
Simone Ernst, Joana Heinzelmann, Rainer M. Bohle, Georg F. Weber, Michael Stöckle, Kerstin Junker, Julia Heinzelbecker
Abstract
BACKGROUND: Seminomatous germ cell tumours (SGCT) are the most frequent malignancy in young men. Reliable prognostic biomarkers for the prediction of metastasis at diagnosis and the risk of relapse in clinical stage I (CSI) are lacking. Adjuvant therapies carry a risk of overtreatment, whereas salvage therapies have a risk of high toxicities. Thus, the identification of reliable prognostic biomarkers is highly desirable to identify patients who will benefit from early adjuvant treatment. MicroRNAs (miRNAs) regulate tumour development and progression, and their potential as biomarkers has already been proven in a variety of malignancies. OBJECTIVES: The aim of our study was to define a specific miRNA expression pattern that discriminates metastatic from non-metastatic primary SGCT. MATERIALS AND METHODS: Total RNA was isolated from 24 formalin-fixed paraffin-embedded (FFPE) primary SGCT tumours (10 non-metastatic, five metachronously and nine synchronously metastatic) and from 10 normal testicular tissue samples. Microarray analysis was performed for global miRNA expression profiling. The results were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Statistical analysis was performed using SPSS. RESULTS: Microarray analyses revealed a specific miRNA pattern that distinguishes metastatic from non-metastatic SGCT. Sixty-three miRNAs were differentially expressed in metastatic compared to non-metastatic tumours (P < .01). Microarray results were confirmed by qRT-PCR for three out of five selected miRNAs (miR-29c-5p, miR-506-3p and miR-371a-5p; P < .05). All five miRNAs (miR-29c-5p, miR-506-3p, miR-1307-5p, miR-371a-5p and miR-371a-3p) showed differential expression between tumour and normal tissues (P < .05). CONCLUSION: Metastatic primary SGCTs are characterized by a specific miRNA expression pattern. Therefore, specific miRNAs could represent a new tool to predict the metastatic potential in SGCT patients.