Signaling pathway perturbation analysis for assessment of biological impact of cigarette smoke on lung cells.
Hongyu Chen, Xi Chen, Yifei Shen, Xinxin Yin, Fangjie Liu, Lu Liu, Jie Yao, Qinjie Chu, Yaqin Wang, Hongyan Qi, Michael P Timko, Weijia Fang, Longjiang Fan
Author Information
Hongyu Chen: Department of Medical Oncology, First Affiliated Hospital, Zhejiang University, Hangzhou, 310058, China.
Xi Chen: Institute of Crop Science, Zhejiang University, Hangzhou, 310058, China.
Yifei Shen: Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Xinxin Yin: Institute of Crop Science, Zhejiang University, Hangzhou, 310058, China.
Fangjie Liu: Institute of Bioinformatics, Zhejiang University, Hangzhou, 310058, China.
Lu Liu: Institute of Crop Science, Zhejiang University, Hangzhou, 310058, China.
Jie Yao: Institute of Bioinformatics, Zhejiang University, Hangzhou, 310058, China.
Qinjie Chu: Institute of Bioinformatics, Zhejiang University, Hangzhou, 310058, China.
Yaqin Wang: Institute of Biotechnology, Zhejiang University, Hangzhou, 310058, China.
Hongyan Qi: Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou, 310058, China.
Michael P Timko: Department of Biology and Public Health Sciences, University of Virginia, Charlottesville, VA, 22904, USA.
Weijia Fang: Department of Medical Oncology, First Affiliated Hospital, Zhejiang University, Hangzhou, 310058, China. weijiafang@zju.edu.cn.
Longjiang Fan: Department of Medical Oncology, First Affiliated Hospital, Zhejiang University, Hangzhou, 310058, China. fanlj@zju.edu.cn.
Exposure to cigarette smoke (CS) results in injury to the epithelial cells of the human respiratory tract and has been implicated as a causative factor in the development of chronic obstructive pulmonary disease and lung cancers. The application of omics-scale methodologies has improved the capacity to understand cellular signaling processes underlying response to CS exposure. We report here the development of an algorithm based on quantitative assessment of transcriptomic profiles and signaling pathway perturbation analysis (SPPA) of human bronchial epithelial cells (HBEC) exposed to the toxic components present in CS. HBEC were exposed to CS of different compositions and for different durations using an ISO3308 smoking regime and the impact of exposure was monitored in 2263 signaling pathways in the cell to generate a total effect score that reflects the quantitative degree of impact of external stimuli on the cells. These findings support the conclusion that the SPPA algorithm provides an objective, systematic, sensitive means to evaluate the biological impact of exposures to CS of different compositions making a powerful comparative tool for commercial product evaluation and potentially for other known or potentially toxic environmental smoke substances.
References
J Contemp Dent Pract. 2019 Jan 1;20(1):101-107
[PMID: 31058621]
