Gene expression signatures prognostic for relapse in stage I testicular germ cell tumours

Abstract

Objectives To identify differentially expressed genes between relapsed and non‐relapsed clinical stage I testicular germ cell tumours (TGCTs). Materials and Methods We reviewed patients with clinical stage I non‐seminoma and seminoma from an institutional database (2000–2012) who were managed by active surveillance. Patients with non‐relapsed non‐seminoma and non‐relapsed seminoma were defined as being relapse‐free after 2 and 3 years of surveillance, respectively. RNA extraction and gene expression analysis was performed on archival primary tumour samples and gene‐set enrichment analysis (GSEA) was conducted in order to identify differentiating biological pathways. Results A total of 57 patients (relapsed non‐seminoma, n = 12; relapsed seminoma, n =15; non‐relapsed non‐seminoma, n = 15; non‐relapsed seminoma, n = 15) were identified, with a median (range) relapse time of 5.6 (2.5–18.1) and 19.3 (4.7–65.3) months in the relapsed non‐seminoma and relapsed seminoma cohorts, respectively. A total of 1 039 differentially expressed genes were identified that separated relapsed and non‐relapsed groups. In patients with relapse, 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 relapsed and non‐relapsed cases was discovered when combining non‐seminoma and seminoma samples using 10‐ and 30‐probe signatures; however, this profile was not observed in the seminoma and non‐seminoma cohorts individually. Conclusion A discriminating signature for relapsed disease was identified for clinical stage I TGCT that we were not able to identify by histology alone. Further validation is required to determine if this signature provides independent prognostic information to standard pathological risk factors.

Development and Validation of a Gene Signature for Prediction of Relapse in Stage I Testicular Germ Cell Tumors

“…Korkola et al identified an eight-gene model that can predict overall survival in patients with TGCTs in 2009, but without validation of RFS ( 34 ). Lewin et al also reported a discriminatory gene expression profile between relapsed and non-relapsed cases on the basis of 10- and 30-gene signatures ( 35 ). However, the prediction score by Lewin et al was limited to a cohort with single histology and lacked validation in large external sets.…”

MicroRNA and transcription factor co-regulatory networks and subtype classification of seminoma and non-seminoma in testicular germ cell tumors

“…Validate of hub molecules. The expression patterns of three types of molecules (TF, miRNA and gene) identified as hubs were evaluated using an independent dataset from GEO (ID: GSE99420) 62 . The original study was to find gene signatures for relapse after 2 and 3 years of surveillance of TGCT.…”

“…S4, and Table 4. Since these hub genes in top 5 FFLs were important for the regulatory mechanism of TGCT, we evaluated their regulatory patterns using a validation dataset (GEO GSE99420) 62 below.…”

Comprehensive characteristics of pathological subtypes in testicular germ cell tumor: Gene expression, mutation and alternative splicing

“…Chang et al evaluated the expression patterns of cancer-testis (CT) genes of TGCT patients in TCGA, and confirmed the role of CT genes in the prognosis of TGCT (51). By retrospectively analyzing the characteristics of patients with stage I TGCT, Lewin identified the differential gene expression profile between patients with relapsed and nonrelapsed TGCT (52). Mallik and his colleagues combined analysis of gene expression and methylation in seminoma and non-seminoma, providing a co-regulation research perspective (13).…”