Chemotherapy-refractory high-grade serous ovarian carcinoma: single-cell findings, TCGA-OV transcriptomic context, and a single-case MRI–transcriptome illustration
- 1Radiology Imaging Center, Nanbai Xiang Hospital Complex, The First Affiliated Hospital of Wenzhou Medical University , , ,
- 2Gynecology Department, The First Affiliated Hospital of Wenzhou Medical University , , ,
Abstract
Background: Primary chemotherapy refractoriness remains a clinical challenge in high-grade serous ovarian carcinoma (HGSC) and may reflect pre-existing tumor-cell states and microenvironmental heterogeneity. We examined public single-cell and bulk transcriptomic resources, a barcode-matched MRI case, and an in vitro cisplatin-perturbation RT-qPCR experiment.
Methods: We reanalyzed GSE300897, comprising 19,156 annotated cells from nine treatment-naïve HGSC biopsy libraries (four chemotherapy-refractory and five chemotherapy-sensitive), with response summaries retained at the library/patient level. The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) provided 421 unique primary tumors for cohort-scale transcriptomic and overall survival context. One TCGA-OV case (TCGA-24-1423) linked a multiparametric MRI examination to a tumor RNA-seq barcode. OVCAR-3 and Caov-3 cells were exposed to cisplatin (5 μM, 24 h), and IFIT1, MX1, SNAI1, and HIF1A expression was measured by RT-qPCR.
Results: Across the nine GSE300897 libraries, no cancer-cell program passed Benjamini–Hochberg (BH) q < 0.05. Refractory libraries showed a lower type-I interferon (IFN-I) score (−0.15 log1p(CP10k)) and epithelial-to-mesenchymal transition (EMT) balance (−0.16), with a small increase in hypoxia (+0.05). In TCGA-OV, none of the six displayed program scores reached BH q < 0.05 in age- and stage-adjusted Cox models; IFN-I tertiles separated nominally by Kaplan–Meier analysis (log-rank p = 0.029), whereas continuous IFN-I was not significant after adjustment (HR = 0.96 per SD, BH q = 0.927). In TCGA-24-1423, the paired transcriptome showed an IFN-I score at the 86.8th TCGA-OV percentile, with IFIT1 and MX1 at the 87.5th and 93.7th percentiles. RT-qPCR showed lower IFIT1/MX1 and higher SNAI1/HIF1A after acute cisplatin exposure in both cell lines (all Holm-adjusted p < 0.05).
Conclusion: These findings support a conservative, hypothesis-generating interpretation of chemotherapy response-associated transcriptional heterogeneity in HGSC. Reduced IFN-I and altered cell-state programs were directional features of the small refractory single-cell cohort, whereas TCGA-OV provided context rather than independent response validation. The MRI-linked case demonstrates imaging–transcriptome pairing but does not establish an imaging biomarker. The RT-qPCR experiment demonstrates cisplatin-responsive changes in selected genes but models acute drug perturbation rather than the pretreatment clinical refractory state.
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BibTeX
@article{chen2026chemotherapyrefractory,
title = {{Chemotherapy-refractory high-grade serous ovarian carcinoma: single-cell findings, TCGA-OV transcriptomic context, and a single-case MRI–transcriptome illustration}},
author = {Litian Chen and Pingping Fu and Sunjie Wu and Ben Chen and Xin Wen},
journal = {Frontiers in genetics},
year = {2026},
month = oct,
doi = {10.3389/fgene.2026.1943981},
url = {https://europepmc.org/article/PMC/PMC13724571},
note = {CC BY},
}
RIS
TY - JOUR
TI - Chemotherapy-refractory high-grade serous ovarian carcinoma: single-cell findings, TCGA-OV transcriptomic context, and a single-case MRI–transcriptome illustration
AU - Litian Chen
AU - Pingping Fu
AU - Sunjie Wu
AU - Ben Chen
AU - Xin Wen
PY - 2026
DA - 2026/10/19
JO - Frontiers in genetics
DO - 10.3389/fgene.2026.1943981
UR - https://europepmc.org/article/PMC/PMC13724571
AB - Background: Primary chemotherapy refractoriness remains a clinical challenge in high-grade serous ovarian carcinoma (HGSC) and may reflect pre-existing tumor-cell states and microenvironmental heterogeneity. We examined public single-cell and bulk transcriptomic resources, a barcode-matched MRI case, and an in vitro cisplatin-perturbation RT-qPCR experiment. Methods: We reanalyzed GSE300897, comprising 19,156 annotated cells from nine treatment-naïve HGSC biopsy libraries (four chemotherapy-refractory and five chemotherapy-sensitive), with response summaries retained at the library/patient level. The Cancer Genome Atlas Ovarian Cancer (TCGA-OV) provided 421 unique primary tumors for cohort-scale transcriptomic and overall survival context. One TCGA-OV case (TCGA-24-1423) linked a multiparametric MRI examination to a tumor RNA-seq barcode. OVCAR-3 and Caov-3 cells were exposed to cisplatin (5 μM, 24 h), and IFIT1, MX1, SNAI1, and HIF1A expression was measured by RT-qPCR. Results: Across the nine GSE300897 libraries, no cancer-cell program passed Benjamini–Hochberg (BH) q < 0.05. Refractory libraries showed a lower type-I interferon (IFN-I) score (−0.15 log1p(CP10k)) and epithelial-to-mesenchymal transition (EMT) balance (−0.16), with a small increase in hypoxia (+0.05). In TCGA-OV, none of the six displayed program scores reached BH q < 0.05 in age- and stage-adjusted Cox models; IFN-I tertiles separated nominally by Kaplan–Meier analysis (log-rank p = 0.029), whereas continuous IFN-I was not significant after adjustment (HR = 0.96 per SD, BH q = 0.927). In TCGA-24-1423, the paired transcriptome showed an IFN-I score at the 86.8th TCGA-OV percentile, with IFIT1 and MX1 at the 87.5th and 93.7th percentiles. RT-qPCR showed lower IFIT1/MX1 and higher SNAI1/HIF1A after acute cisplatin exposure in both cell lines (all Holm-adjusted p < 0.05). Conclusion: These findings support a conservative, hypothesis-generating interpretation of chemotherapy response-associated transcriptional heterogeneity in HGSC. Reduced IFN-I and altered cell-state programs were directional features of the small refractory single-cell cohort, whereas TCGA-OV provided context rather than independent response validation. The MRI-linked case demonstrates imaging–transcriptome pairing but does not establish an imaging biomarker. The RT-qPCR experiment demonstrates cisplatin-responsive changes in selected genes but models acute drug perturbation rather than the pretreatment clinical refractory state.
SN - 1664-8021
ER -