Dataset Information

Discriminating metastasised from non-metastasised seminoma based on transcriptional changes in primary tumours using NGS.

ABSTRACT: BACKGROUND: We aimed to better discriminate (occult) metastasised from non-metastasised seminoma based on transcriptional changes of small RNAs in the primary tumour. METHODS: Total RNAs including small RNAs were isolated from five testicular tumours of each, lymphogenic, occult and non-metastasised patients. Next-generation sequencing (SOLID, Life Technologies) was used to examine transcriptional changes. Small RNAs showing ⩾50 reads and a significant ⩾2-fold difference using non-metastasised tumours as the reference group were examined in univariate logistic regression analysis and combinations of two small RNAs were further examined using support vector machines. RESULTS: On average, 1.3 × 10(7), 1.4 × 10(7) and 1.7 × 10(7) small RNA reads were detectable in non-metastasised, occult and lymphogenic metastasised seminoma, respectively, of which 30-32% remained after trimming. Between 59 and 68% represented annotated reads and between 8.6 and 11% were annotated small RNA tags. Of them, 137 small RNAs showed>50 reads and a two-fold difference to the reference. In univariate analysis, 32-38 small RNAs significantly discriminated lymphogenic/occult from non-metastasised seminoma, and among these different comparisons, it were the same small RNAs in 51-88%. Many combinations of two of these small RNAs allowed a complete discrimination of metastasised from non-metastasised seminoma irrespective of the metastasis subtype. CONCLUSIONS: Metastasised and non-metastasised seminoma can be completely discriminated with a combination of two small RNAs.

SUBMITTER: Ruf CG

PROVIDER: S-EPMC4037819 | biostudies-other | 2014 May

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BackgroundTesticular germ cell tumours are the most frequent cancer of young men with an increasing incidence all over the world. Pathogenesis and reasons of this increase remain unknown but epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs) with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, these EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. Several research groups recently showed that the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30) mediates the effects of estrogens and several xenoestrogens through rapid non genomic activation of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium). The aim of this study was to demonstrate that GPER was overexpressed in testicular tumours and was able to trigger JKT-1 seminoma cell proliferation.ResultsWe report here for the first time a complete morphological and functional characterization of GPER in normal and malignant human testicular germ cells. In normal adult human testes, GPER was expressed by somatic (Sertoli cells) and germ cells (spermatogonia and spermatocytes). GPER was exclusively overexpressed in seminomas, the most frequent testicular germ cell cancer, localized at the cell membrane and triggered a proliferative effect on JKT-1 cells in vitro, which was completely abolished by G15 (a GPER selective antagonist) and by siRNA invalidation.ConclusionThese results demonstrate that GPER is expressed by human normal adult testicular germ cells, specifically overexpressed in seminoma tumours and able to trigger seminoma cell proliferation in vitro. It should therefore be considered rather than classical ERs when xeno-estrogens or other endocrine disruptors are assessed in testicular germ cell cancers. It may also represent a prognosis marker and/or a therapeutic target for seminomas.

Dataset Information

Discriminating metastasised from non-metastasised seminoma based on transcriptional changes in primary tumours using NGS.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets