In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. 528-528
Kurzfassung:
528 Background: Up to 40% of pure seminomatous germ cell tumors (GCTs) are clinically metastasized at initial diagnosis. Additionally, up to 20% of patients have occult metastasis but are not diagnosed due to missing markers. We hypothesize that pure seminomatous GCTs differ from metastasized to non-metastasized patients, possibly owing to differences in tumor heterogeneity. Since in few other tumor types genes linked to metastasis are shown to be more often upregulated at the tumor front, we investigated different regions of seminomas in non-metastasized and metastasized patients. Methods: Seminoma patient samples without metastasis, with no adjuvant therapy, and with recurrence-free follow-up of at least two years (n = 21), and patients showing metastasis (n = 14) were selected for the study. Based on formalin-fixed paraffin embedded tissues, the tumor front (TF) and tumor center (TC) regions of each patient were determined and separately collected using laser capture microdissection. RNA was extracted and a multiplex gene expression analysis was performed on all TF and TC samples using nCounter technology of Nanostring. A panel of 770 transcripts was analyzed using the PanCancer Progression panel. Different bioinformatics tools were employed for analyzing the expression data. Results: Hierarchical cluster analysis showed no differential gene clustering between metastasized and non-metastasized patients. Comparing TF and TC in the metastasized group more genes (29 genes) were significantly differentially expressed (log2 fold change 〉 1.5, FDR 〈 0.05) compared to cSI patients (12 genes). Pairwise comparison of TF and TC for each individual patient showed differential expression of genes in these two regions. Lasso regression analysis of TC could not reveal any signature to predict metastasis. However, with respect to the TF a signature of only six genes was sufficient to predict metastasis with a specificity of 100%, and a sensitivity of 92.9%. Conclusions: This study describes tumor heterogeneity in seminomas and identifies a gene signature that could predict metastasis and has to be validated on occult metastasized seminomatous patients.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2019.37.7_suppl.528
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2019
ZDB Id:
2005181-5
