Single-cell transcriptomes reveal the mechanism for a breast cancer prognostic gene panel

// Shengwen Calvin Li 1 , Andres Stucky 2 , Xuelian Chen 2 , Mustafa H. Kabeer 3 , William G. Loudon 4 , Ashley S. Plant 5 , Lilibeth Torno 6 , Chaitali S. Nangia 7 , Jin Cai 8 , Gang Zhang 9 and Jiang F. Zhong 2 1 Neuro-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 2 Division 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 3 Pediatric Surgery, CHOC Children's Hospital, Department of Surgery, University of California-Irvine School of Medicine, Orange, CA, USA 4 Neuroscience 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 5 Division of Pediatric Oncology, Children’s Hospital of Orange County, Orange, CA, USA 6 Hyundai 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 7 Chan Soon-Shiong Institute for Medicine, Verity Medical Foundation, Laguna Hills, CA, USA 8 Department of Oral and Maxillofacial Surgery, Zhuhai People’s Hospital, Zhuhai, China 9 Department of Oral and Maxillofacial Surgery, Xinqiao Hospital, Army Medical University, Chongqing, China Correspondence to: Shengwen Calvin Li, email: shengwel@uci.edu Jin Cai, email: caijin70@163.com Gang Zhang, email: xqyykqk@163.com 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 ABSTRACT 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.