NanoString profiling of DNA repair and apoptosis genes in testicular germ cell tumours with divergent chemotherapy outcomes
- Author(s)
- Hitchen, N; Bedard, PL; Winegarden, N; Sweet, J; Grubb, A; Anson-Cartwright, L; Chung, P; Warde, P; MOORE, M; Kwan, EM; Tran, B;
- Journal Title
- Therapeutic Advances in Medical Oncology
- Publication Type
- Aug 26
- Abstract
- BACKGROUND: Platinum-based chemotherapy cures most patients with advanced testicular germ cell tumours (TGCTs), yet a subset develops resistance or relapse. The molecular basis of platinum sensitivity and resistance remains unclear, particularly in archival formalin-fixed paraffin-embedded (FFPE) samples that limit broad genomic analyses. OBJECTIVES: To evaluate whether differential expression of genes involved in apoptosis, DNA repair, and cell-cycle regulation distinguish platinum-resistant TGCTs. DESIGN: Retrospective exploratory molecular profiling study using archival TGCT tissue specimens. METHODS: We profiled the expression of 30 genes related to apoptosis, DNA repair, and cell cycle regulation in 50 archival TGCT samples from 41 patients using the NanoString nCounter platform. Samples included platinum-sensitive, platinum-resistant, and post-chemotherapy teratomas. Platinum-resistant disease was defined as radiological progression and/or rising tumour markers after first line platinum-based chemotherapy. Platinum-sensitive cases included patients achieving complete response as well as those with residual teratoma requiring post-chemotherapy resection. Differential expression analysis and principal component analysis (PCA) were performed to compare transcriptional patterns across groups. RESULTS: Post-chemotherapy teratomas demonstrated a distinct expression profile, characterised by lower POU5F1 (encodes OCT4 protein) expression and higher levels of apoptosis and cell-cycle related genes. In contrast, platinum-resistant and platinum-sensitive primary TGCTs showed substantial overlap in global expression patterns, and no individual gene met thresholds for differential expression. These findings suggest that the transcriptional features of teratoma differentiation are readily detectable with targeted profiling, while platinum resistance is not captured by this gene set. CONCLUSIONS: NanoString-based targeted expression profiling identifies biologically distinct expression patterns in post-chemotherapy teratomas but did not reveal a unifying transcriptional signature associated with platinum resistance in TGCTs. These negative results underscore the multifactorial and heterogenous nature of platinum resistance and highlight the need for broader genomic, immune and epigenomic profiling to better elucidate mechanisms of platinum resistance.; Most people with advanced testicular cancer are cured with platinum-based chemotherapy, but a small group of patients do not respond well or their cancer comes back. This study looked at whether differences in gene activity could explain why some tumours are sensitive to treatment while others are resistant. Researchers analysed stored tumour samples from patients using a method that measures the activity of specific genes involved in DNA repair, cell death (apoptosis) and cell growth. They compared three groups: treatment-sensitive cancers, treatment-resistant cancers and a type of tumour called teratoma that is known to resist chemotherapy. They found that teratomas had a clearly different pattern of gene activity, consistent with their more mature and less aggressive biology. However, there was no clear gene activity differences between chemotherapy-sensitive and chemotherapy-resistant cancers. This suggests that chemotherapy resistance in testicular cancer is complex and likely not caused by changes in a small set of genes. Future research will need broader approaches, looking at the whole genome, immune system and other biological factors to better understand and predict treatment resistance.; eng
- Publisher
- Sage Journals
- Keywords
- nanostring; platinum-resistant; testicular cancer; testicular germ cell
- Research Division(s)
- Personalised Oncology
- Publisher's Version
- https://doi.org/10.1177/17588359261475672
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-09-07 09:09:46
Last Modified: 2026-09-07 09:09:58