Gene Expression Signatures Prognostic for Relapse in Stage I Testicular Germ Cell Tumors (TGCT)

ABSTRACT: Design, Setting and Participants We reviewed patients with SI non-seminoma (NS) and seminoma (S) from an institutional database (2000-2012) managed with active surveillance. NR-NS and NR-S patients were defined as having no evidence of relapse after 2 and 3 years of surveillance respectively. RNA extraction and gene expression analysis was performed on archival primary tumor samples. Outcome measurements and statistical analysis Gene-Set-Enrichment-Analysis (GSEA) was conducted in order to identify discriminating biological pathways associated with differentiation of R from NR and S from NS. Hierarchical clustering analysis and Wilcoxon testing were used to evaluate candidate genes and expression patterns that could differentiate NR from R. Results 57 patients (12 R-NS, 15 RS, 15 NR-NS, 15 NR-S) were identified with median relapse time of 5.6 (2.5-18.1) and 19.3 (4.7-65.3) months in NS and S cohorts respectively. 1039 differential expressed genes were identified that separated R and NR. In R patients, GSEA revealed enrichment in pathways associated with differentiation such as skeletal development (i.e. FGFR1, BMP4, GLI2, SPARC, COL2A1), tissue (i.e. BMP4, SPARC, COL13A1) and bone remodelling (i.e. CARTPT, GLI2, MGP). A discriminative gene expression profile between R and NR cases was discovered when combining NS and S samples using 10 (p=0.03) and 30 (p=0.03) probe signatures. However, this profile was not observed in the S and NS cohorts individually. Conclusions A discriminating signature for R and NR was identified for SI TGCT that was not histology specific. Genes associated with active differentiation were enriched in patients with R disease. Further validation is required to determine if this signature provides independent prognostic information to standard pathological risk factors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE99420 | GEO | 2018/05/21

REPOSITORIES: GEO