A gene signature completely identifies metastasized testis tumors

Abstract

22144 Background: Selection of gene targets to distinguish metastasized from non-metastasized seminoma. Methods: Total RNA was isolated from metastasized seminoma (n=10, T1–3N0M0 to T1N1–2M0), non-metastasized seminoma (n=21) and corresponding normal tissues. The RNA from 10 biopsies of each tissue type was pooled and separately hybridized on four whole genome microarrays (Human Genome Survey Microarray V2.0, Applied Biosystem) for screening purposes. 92 selected gene candidates were then quantitatively examined using RTQ-PCR. Results: Agreement in gene expression was 88% between the whole genome microarrays and RTQ-PCR. Metastasized seminoma showed 1,912 upregulated and 2,179 downregulated genes with ≥ 2-fold differences in gene expression as compared to non-metastasized seminoma. The number of upregulated genes coding for immunity and defense, cell signaling and developmental processes were significantly overrepresented. RTQ-PCR showed that mean gene expression values of the 92 genes in general were significantly reduced in metastasized compared to non-metastasized seminoma. The presence of metastases could be completely predicted (100% specificity) based on a 85-gene expression signature by using Logistic Regression. Accompanied sensitivity and accuracy of the 10-fold crossvalidation model were 77.8% and 84.2%, respectively. Conclusions: A logistic regression model using the 85 gene expression signature allowed complete identification of metastasized seminoma. No significant financial relationships to disclose.