A1 Refereed original research article in a scientific journal
Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer
Authors: Zhang Kaiyang, Erkan Erdogan Pekcan, Jamalzadeh Sanaz, Dai Jun, Andersson Noora, Kaipio Katja, Lamminen Tarja, Mansuri Naziha, Huhtinen Kaisa, Carpén Olli, Hietanen Sakari, Oikkonen Jaana, Hynninen Johanna, Virtanen Anni, Häkkinen Antti, Hautaniemi Sampsa, Vähärautio Anna
Publisher: AMER ASSOC ADVANCEMENT SCIENCE
Publication year: 2022
Journal: Science Advances
Journal name in source: SCIENCE ADVANCES
Journal acronym: SCI ADV
Article number: eabm1831
Volume: 8
Issue: 8
Number of pages: 18
ISSN: 2375-2548
DOI: https://doi.org/10.1126/sciadv.abm1831
Web address : https://www.science.org/doi/10.1126/sciadv.abm1831
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/175009671
Chemotherapy resistance is a critical contributor to cancer mortality and thus an urgent unmet challenge in oncology. To characterize chemotherapy resistance processes in high-grade serous ovarian cancer, we prospectively collected tissue samples before and after chemotherapy and analyzed their transcriptomic profiles at a single-cell resolution. After removing patient-specific signals by a novel analysis approach, PRIMUS, we found a consistent increase in stress-associated cell state during chemotherapy, which was validated by RNA in situ hybridization and bulk RNA sequencing. The stress-associated state exists before chemotherapy, is subclonally enriched during the treatment, and associates with poor progression-free survival. Co-occurrence with an inflammatory cancer-associated fibroblast subtype in tumors implies that chemotherapy is associated with stress response in both cancer cells and stroma, driving a paracrine feed-forward loop. In summary, we have found a resistant state that integrates stromal signaling and subclonal evolution and offers targets to overcome chemotherapy resistance.
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