Longitudinal single-cell RNA-seq analysis reveals stress-promoted chemoresistance in metastatic ovarian cancer

• DOI: 10.1126/sciadv.abm1831
• Publication Date: 2022-02-23T18:59:33Z
• Authors: Kaiyang Zhang; Erdogan Pekcan Erkan; Sanaz Jamalzadeh; Jun Dai; Noora Andersson; Katja Kaipio; Tarja Lamminen; Naziha Mansuri; Kaisa Huhtinen; Olli Carpén; Sakari Hietanen; Jaana Oikkonen; Johanna Hynninen; Anni Virtanen; Antti Häkkinen; Sampsa Hautaniemi; Anna Vähärautio
• Keywords: Single-Cell Analysis

Chemotherapy resistance is a critical contributor to cancer mortality and thus an urgent unmet challenge in oncology. To characterize chemotherapy processes high-grade serous ovarian cancer, we prospectively collected tissue samples before after analyzed their transcriptomic profiles at single-cell resolution. After removing patient-specific signals by novel analysis approach, PRIMUS, found consistent increase stress-associated cell state during chemotherapy, which was validated RNA situ hybridization bulk sequencing. The exists subclonally enriched the treatment, associates with poor progression-free survival. Co-occurrence inflammatory cancer–associated fibroblast subtype tumors implies that associated stress response both cells stroma, driving paracrine feed-forward loop. In summary, have resistant integrates stromal signaling subclonal evolution offers targets overcome resistance.