Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
Bioinformatics and Computational Genomics Laboratory, Princess Margaret Cancer Centre, Toronto, ON, Canada.
BJU Int. 2018 Nov;122(5):814-822. doi: 10.1111/bju.14372. Epub 2018 May 31.
To identify differentially expressed genes between relapsed and non-relapsed clinical stage I testicular germ cell tumours (TGCTs).
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.
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.
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.
鉴定复发与非复发临床 I 期睾丸生殖细胞肿瘤（TGCT）之间差异表达的基因。
我们回顾了机构数据库（2000-2012 年）中接受主动监测的临床 I 期非精原细胞瘤和精原细胞瘤患者的资料。无复发非精原细胞瘤和无复发精原细胞瘤患者分别定义为在监测 2 年和 3 年后无复发。对存档的原发肿瘤样本进行 RNA 提取和基因表达分析，并进行基因集富集分析（GSEA）以鉴定有区别的生物学途径。
共鉴定出 57 例患者（复发非精原细胞瘤，n=12；复发精原细胞瘤，n=15；无复发非精原细胞瘤，n=15；无复发精原细胞瘤，n=15），复发非精原细胞瘤和复发精原细胞瘤组的中位（范围）复发时间分别为 5.6（2.5-18.1）和 19.3（4.7-65.3）个月。鉴定出 1039 个差异表达基因，可将复发组和非复发组分开。在复发患者中，GSEA 显示与分化相关的途径富集，如骨骼发育（即 FGFR1、BMP4、GLI2、SPARC、COL2A1）、组织（即 BMP4、SPARC、COL13A1）和骨重塑（即 CARTPT、GLI2、MGP）。当使用 10 个和 30 个探针特征组合非精原细胞瘤和精原细胞瘤样本时，发现了复发和非复发病例之间具有区别的基因表达谱；然而，在精原细胞瘤和非精原细胞瘤组中均未观察到该谱。
我们发现了一种用于临床 I 期 TGCT 的复发疾病的鉴别特征，单凭组织学无法识别。需要进一步验证该特征是否为标准病理危险因素提供独立的预后信息。
