Cancer stem cell transcriptomic signatures reveal patient-to-patient heterogeneity emphasizing the need for patient-specific ovarian cancer targets
- 1Korea Institute of Science and Technology
Abstract
Background/Objectives: In high-grade serous ovarian cancer (HGSOC), the abilities of tumor cells to resist cytotoxic treatment and relapse are largely driven by ovarian cancer stem cells (CSCs). CSCs are a population of cells within a tumor that maintain stem-like qualities and have the capacity to produce metastasis and drive drug resistance. Based on the complexity of CSC signaling and emerging evidence of differential isoform usage in development, we hypothesize that CSCs possess a patient-specific, heterogeneous landscape which exploits isoform diversity to sustain stemness, metastasis and drug resistance. Methods: RNA-seq was generated from 3 patient-derived HGSOC (PD-HGSOC) to investigate stemness and differentiation status comparing standard culture and CSCs. The data was analyzed at both gene- and isoform-levels to identify patient-specific CSC features and define mechanisms of cancer-related stemness and plasticity. Results: CSCs exhibited higher stemness characteristics and identified differentially expressed gene sets across PD-HGSOCs. We noted that each patient had a distinct subset of genes regulating stemness phenotypes which suggested multiple mechanisms of CSC development and maintenance. Additionally, a large proportion of gene-level expression changes were driven by the differential expression of a single predominant isoform. Importantly, our isoform-level analysis enabled the identification of differential isoform usage that would not be detected with gene level expression analysis. Conclusions: CSC phenotypes such as chemoresistance, metastasis and self-renewal are conserved across patients, but arise from largely patient-specific gene and isoform programs. This CSC heterogeneity is reflective of the heterogeneity seen in patients and should be further evaluated in deriving precision-medicine approaches for HGSOC.
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BibTeX
@misc{jung2026cancer,
title = {{Cancer stem cell transcriptomic signatures reveal patient-to-patient heterogeneity emphasizing the need for patient-specific ovarian cancer targets}},
author = {M. S. Jung and L. J. Davis and A. A. Birdwell and J. Kang and C. Feng and A. Pi and S. C. Lee and S. Davern and R. P. McCord and J. Yue and W. Zhang and W.-Y. Choi and R. S. Perkins},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.30.755773},
url = {https://www.biorxiv.org/content/10.64898/2026.09.30.755773v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Cancer stem cell transcriptomic signatures reveal patient-to-patient heterogeneity emphasizing the need for patient-specific ovarian cancer targets
AU - M. S. Jung
AU - L. J. Davis
AU - A. A. Birdwell
AU - J. Kang
AU - C. Feng
AU - A. Pi
AU - S. C. Lee
AU - S. Davern
AU - R. P. McCord
AU - J. Yue
AU - W. Zhang
AU - W.-Y. Choi
AU - R. S. Perkins
PY - 2026
DA - 2026/09/30
PB - bioRxiv
DO - 10.64898/2026.09.30.755773
UR - https://www.biorxiv.org/content/10.64898/2026.09.30.755773v1
AB - Background/Objectives: In high-grade serous ovarian cancer (HGSOC), the abilities of tumor cells to resist cytotoxic treatment and relapse are largely driven by ovarian cancer stem cells (CSCs). CSCs are a population of cells within a tumor that maintain stem-like qualities and have the capacity to produce metastasis and drive drug resistance. Based on the complexity of CSC signaling and emerging evidence of differential isoform usage in development, we hypothesize that CSCs possess a patient-specific, heterogeneous landscape which exploits isoform diversity to sustain stemness, metastasis and drug resistance. Methods: RNA-seq was generated from 3 patient-derived HGSOC (PD-HGSOC) to investigate stemness and differentiation status comparing standard culture and CSCs. The data was analyzed at both gene- and isoform-levels to identify patient-specific CSC features and define mechanisms of cancer-related stemness and plasticity. Results: CSCs exhibited higher stemness characteristics and identified differentially expressed gene sets across PD-HGSOCs. We noted that each patient had a distinct subset of genes regulating stemness phenotypes which suggested multiple mechanisms of CSC development and maintenance. Additionally, a large proportion of gene-level expression changes were driven by the differential expression of a single predominant isoform. Importantly, our isoform-level analysis enabled the identification of differential isoform usage that would not be detected with gene level expression analysis. Conclusions: CSC phenotypes such as chemoresistance, metastasis and self-renewal are conserved across patients, but arise from largely patient-specific gene and isoform programs. This CSC heterogeneity is reflective of the heterogeneity seen in patients and should be further evaluated in deriving precision-medicine approaches for HGSOC.
ER -