Circulating microRNAs as biomarkers to assist the management of the malignant germ-cell-tumour subtype choriocarcinoma

Translational Oncology

Dawn Ward¹  Stephen Smith²  Nicholas Coleman³  Cinzia G. Scarpini⁴  Lorena Verduci⁴  Matthew J. Murray⁴  James C. Nicholson⁴ 

[1] Corresponding authors at: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.;Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom;Department of Paediatric Haematology and Oncology, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 0QQ, United Kingdom;Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom;

关键词: C19MC;    Choriocarcinoma;    Germ-cell-tumour;    Human-chorionic-gonadotrophin;    Mediastinal;    miRNA;   

DOI  :  

来源: DOAJ

【 摘 要 】

Germ-cell-tumours (GCTs) are heterogeneous and management is complex. The current conventional biomarkers, alpha-fetoprotein and human-chorionic-gonadotropin (HCG), have limited utility for diagnosis/follow-up as secretion is restricted to specific malignant-GCT subtypes and long half-life can make interpretation and clinical decision-making challenging. We sought to identify circulating microRNAs that reflected choriocarcinoma disease activity more accurately than HCG in a metastatic primary mediastinal nonseminomatous-GCT (PMNSGCT) case with elevated diagnostic serum HCG (>250,000 U/L), consistent with pure choriocarcinoma. We undertook comprehensive microRNA profiling (n = 754 microRNAs) using two 384-well TaqMan Low-Density-Array cards in 16 serum samples; 10 from PMNSGCT diagnosis/follow-up and six controls. Key findings underwent confirmatory qRT-PCR. We identified a serum panel of choriocarcinoma-specific ‘chromosome-19-microRNA-cluster’ (C19MC) microRNAs that were highly elevated at diagnosis but fell rapidly on treatment and normalised before the second full chemotherapy course. We also re-confirmed serum elevation of the previously identified malignant-GCT marker miR-371a-3p at diagnosis. These circulating microRNA markers reflected choriocarcinoma disease activity more accurately than serum HCG and real-time knowledge would have assisted clinical decision-making. With further study, these microRNA markers will facilitate future management of such patients and are likely to result in improved outcomes.

【 授权许可】

Unknown