Single-cell transcriptomes reveal the mechanism for a breast cancer prognostic gene panel
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Shengwen Calvin Li1, Andres Stucky2, Xuelian Chen2, Mustafa H. Kabeer3, William G. Loudon4, Ashley S. Plant5, Lilibeth Torno6, Chaitali S. Nangia7, Jin Cai8, Gang Zhang9 and Jiang F. Zhong2
1Neuro-oncology and Stem Cell Research Laboratory, CHOC Children's Research Institute, Children’s Hospital of Orange County; Department of Neurology, University of California-Irvine School of Medicine, Orange, CA, USA
2Division of Periodontology, Diagnostic Sciences and Dental Hygiene, and Division of Biomedical Sciences, Herman Ostrow School of Dentistry, University of Southern California, Los Angeles, CA, USA
3Pediatric Surgery, CHOC Children's Hospital, Department of Surgery, University of California-Irvine School of Medicine, Orange, CA, USA
4Neuroscience Institute, Children's Hospital of Orange County (CHOC), Gamma Knife Center of Southern California, Department of Neurosurgery, University of California-Irvine School of Medicine, Orange, CA, USA
5Division of Pediatric Oncology, Children’s Hospital of Orange County, Orange, CA, USA
6Hyundai Cancer Institute at CHOC Children's Hospital, Oncology, Bone and Soft Tissue Tumor Program, After Cancer Treatment Survivorship Program, CHOC Children's Hospital, Orange, CA, USA
7Chan Soon-Shiong Institute for Medicine, Verity Medical Foundation, Laguna Hills, CA, USA
8Department of Oral and Maxillofacial Surgery, Zhuhai People’s Hospital, Zhuhai, China
9Department of Oral and Maxillofacial Surgery, Xinqiao Hospital, Army Medical University, Chongqing, China
Shengwen Calvin Li, email: [email protected]
Jin Cai, email: [email protected]
Gang Zhang, email: [email protected]
Keywords: cell cycle; single-cell; cell-cycle-staged therapy; transcriptome; cell cycle phase
Abbreviations: CGED: Cancer gene expression database; COSMIC: Catalogue of Somatic Mutations in Cancer; NEJM: New England Journal of Medicine; TCGA: The Cancer Genome Atlas
Received: January 10, 2018 Accepted: August 13, 2018 Published: September 07, 2018
The clinical benefits of the MammaPrint® signature for breast cancer is well documented; however, how these genes are related to cell cycle perturbation have not been well determined. Our single-cell transcriptome mapping (algorithm) provides details into the fine perturbation of all individual genes during a cell cycle, providing a view of the cell-cycle-phase specific landscape of any given human genes. Specifically, we identified that 38 out of the 70 (54%) MammaPrint® signature genes are perturbated to a specific phase of the cell cycle. The MammaPrint® signature panel derived its clinical prognosis power from measuring the cell cycle activity of specific breast cancer samples. Such cell cycle phase index of the MammaPrint® signature suggested that measurement of the cell cycle index from tumors could be developed into a prognosis tool for various types of cancer beyond breast cancer, potentially improving therapy through targeting a specific phase of the cell cycle of cancer cells.
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