Serial single-cell RNA sequencing unveils drug resistance and metastatic traits in stage IV breast cancer

Metastasis is a complex process that remains poorly understood at the molecular levels. We profiled single-cell transcriptomic, genomic, and epigenomic changes associated with cancer cell progression, chemotherapy resistance, and metastasis from a Stage IV breast cancer patient. Pretreatment- and po...

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Bibliographic Details
Published in:NPJ precision oncology 2024-10, Vol.8 (1), p.222-15, Article 222
Main Authors: Otsuji, Kazutaka, Takahashi, Yoko, Osako, Tomo, Kobayashi, Takayuki, Takano, Toshimi, Saeki, Sumito, Yang, Liying, Baba, Satoko, Kumegawa, Kohei, Suzuki, Hiromu, Noda, Tetsuo, Takeuchi, Kengo, Ohno, Shinji, Ueno, Takayuki, Maruyama, Reo
Format: Article
Language:English
Subjects:
631/67/1347
631/67/322
Biopsy
Breast cancer
Cancer Research
Cancer therapies
Cells
Chemotherapy
Cloning
Drug resistance
Estrogens
Gene expression
Gene Therapy
Human Genetics
Internal Medicine
Medical research
Medicine
Medicine & Public Health
Metastasis
Oncology
Transcription factors
Tumors
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Summary:Metastasis is a complex process that remains poorly understood at the molecular levels. We profiled single-cell transcriptomic, genomic, and epigenomic changes associated with cancer cell progression, chemotherapy resistance, and metastasis from a Stage IV breast cancer patient. Pretreatment- and posttreatment-specimens from the primary tumor and distant metastases were collected for single-cell RNA sequencing and subsequent cell clustering, copy number variation (CNV) estimation, transcriptomic factor estimation, and pseudotime analyses. CNV analysis revealed that a small population of pretreatment cancer cells resisted chemotherapy and expanded. New clones including Metastatic Precursor Cells (MPCs), emerged in the posttreatment primary tumors in CNV similar to metastatic cells. MPCs exhibited expression profiles indicative of epithelial–mesenchymal transition. Comparison of MPCs with metastatic cancer cells also revealed dynamic changes in transcription factors and calcitonin pathway gene expression. These findings demonstrate the utility of single-patient clinical sample analysis for understanding tumor drug resistance, regrowth, and metastasis.
ISSN:2397-768X
2397-768X
DOI:10.1038/s41698-024-00723-6