Single‑cell RNA sequencing and cell–cell communication analysis reveal tumor microenvironment associated with chemotherapy responsiveness in ovarian cancer
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Xiaoyan Jiang [2] ; Ningxuan Chen [2] ; Qinglv Wei [1] ; Xin Luo [2] ; Xiaoyi Liu [2] ; Lingcui Xie [2] ; Ping Yi [2] ; Jing Xu [2]
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[1] Chongqing Medical University
Chongqing Medical University
China
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[2] Department of Obstetrics and Gynecology, The Third Afliated Hospital of Chongqing Medical University, Chongqing 401120, China
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- Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 27, Nº. 3, 2025, págs. 1000-1012
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
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Resumen
Background To investigate the impact of the tumor microenvironment (TME) on the responsiveness to chemotherapy in ovarian cancer (OV).
Methods We integrated single cell RNA-seq datasets of OV containing chemo-response information, and characterize their clusters based on diferent TME sections. We focus on analyzing cell–cell communication to elaborate on the mechanisms by which diferent components of the TME directly infuence the chemo-response of tumor cells.
Results scRNA-seq datasets were annotated according to specifc markers for diferent cell types. Diferential analysis of malignant epithelial cells revealed that chemoresistance was associated with the TME. Notably, distinct TME components exhibited varying efects on chemoresistance. Enriched SPP1+ tumor-associated macrophages in chemo-resistant patients could promote chemoresistance through SPP1 binding to CD44 on tumor cells. Additionally, the overexpression of THBS2 in stromal cells could promote chemoresistance through binding with CD47 on tumor cells. In contrast, GZMA in the lymphocytes could downregulate the expression of PARD3 through direct interaction with PARD3, thereby attenuating chemoresistance in tumor cells.
Conclusion Our study indicates that the non-tumor cell components of the TME (e.g. SPP1+ TAMs, stromal cells and lymphocytes) can directly impact the chemo-response of OV and targeting the TME was potentially crucial in chemotherapy of OV.
