Small RNAs in the peripheral blood discriminate metastasized from non-metastasized seminoma

Molecular Cancer

Research

Michael Abend¹  Viktor Meineke¹  Matthias Port²  Hans-Ulrich Schmelz³  Daniela Dinger⁴  Walter Wagner⁴  Cord Matthies⁴  Christian G Ruf⁵  Bertram Müller-Myhsok⁶ 

[1] Bundeswehr Institute of Radiobiology, 80937, Munich, Germany;Bundeswehr Institute of Radiobiology, 80937, Munich, Germany;Department of Hematology, Hemostasis Oncology and Stem Cell Transplantation, MHH, Hannover, Germany;Bundeswehr Institute of Radiobiology, 80937, Munich, Germany;Department of Urology, Federal Armed Forces Central Hospital, 56072, Koblenz, Germany;Department of Urology, Federal Armed Forces Hospital, 22049, Hamburg, Germany;Department of Urology, Federal Armed Forces Hospital, 22049, Hamburg, Germany;Bundeswehr Institute of Radiobiology, 80937, Munich, Germany;Max Planck Institute of Psychiatry, Munich, Germany;

关键词: Testis tumour;    Gene expression;    Small RNA;    MicroRNA;    Metastasized seminoma;    Next generation sequencing;    Risk factor;    Tumour marker;    Blood;   

DOI  :  10.1186/1476-4598-13-47

 received in 2013-12-15, accepted in 2014-02-24,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundWe aimed to better discriminate metastasized (lymphogen/occult/both combined) from non-metastasized seminoma based on post-transcriptional changes examined in the peripheral blood.MethodsTotal RNAs including small RNAs were isolated from the peripheral blood of patients suffering from metastasized testicular tumours (lymphogen, n = 5, clinical stage IIb/c; occult, n = 5, clinical stage I) and non-metastasized patients (n = 5, clinical stage I). Small RNA next generation sequencing (SOLID, Life Technologies) was employed to examine post-transcriptional changes. We searched for small RNAs showing at least 50 reads and a significant ≥ 2-fold difference using peripheral blood small RNAs of non-metastasized tumours as the reference group. Candidate small RNAs were examined in univariate logistic regression analysis and combinations of two small RNAs were further examined using support vector machines.ResultsOn average 1.3x107, 1.2x107 and 1.2x107 small RNA reads were detectable in non-metastasized, lymphogen and occult metastasized seminoma, respectively of which 73-76% remained after trimming. From these between 80-82% represented annotated reads and 7.2-7.8% (1.6-1.7x104) were annotated small RNA tags. Of them 137 small RNAs showed > 50 reads and a ≥ two-fold difference to the reference. In univariate analysis we detected 33-35 different small RNAs which significantly discriminated lymphogen/occult/combined metastasized from non-metastasized seminoma and among these different comparisons it were the same small RNAs in 44-79%. Many combinations of two of these small RNAs completely discriminated metastasized from non-metastasized seminoma irrespective of the metastasis subtype.ConclusionsMetastasized (either lymphogen or occult) seminoma can be completely discriminated from non-metastasized seminoma with a combination of two small RNAs measured in the peripheral blood.

【 授权许可】

CC BY   
© Ruf et al.; licensee BioMed Central Ltd. 2014