Genome-Level Longitudinal Expression of Signaling Pathways and Gene Networks in Pediatric Septic Shock
We have conducted longitudinal studies focused on the expression profiles of signaling pathways and gene networks In children with septic shock. Genome-level expression profiles were generated from whole blood-derived RNA of children with septic shock (n = 30) corresponding to day one and day three of septic shock, respectively. Based on sequential statistical and expression filters, day one and day three of septic shock were characterized by differential regulation of 2,142 and 2,504 gene probes, respectively, relative to controls (n = 15). Venn analysis demonstrated 239 unique genes in the day one dataset, 598 unique genes in the day three dataset, and 1,906 genes common to both datasets. Functional analyses demonstrated time-dependent, differential regulation of genes involved in multiple signaling pathways and gene networks primarily related to immunity and inflammation. Notably, multiple and distinct gene networks involving T cell- and MHC antigen-related biology were persistently downregulated on both day one and day three. Further analyses demonstrated large scale, persistent downregulation of genes corresponding to functional annotations related to zinc homeostasis. These data represent the largest reported cohort of patients with septic shock subjected to longitudinal genome-level expression profiling. The data further advance our genome-level understanding of pediatric septic shock and support novel hypotheses.
Additional Genomics of Pediatric SIRS/Septic Shock Investigators: Robert J. Freishtat, M.D., M.P.H., (Children’s National Medical Center, Washington, D.C.); Mary Ann Tagavilla, M.D. (Cincinnati Children’s Hospital Medical Center, Cincinnati, OH); Julie Simon, R.N. (Children’s Hospital and Research Center Oakland, Oakland, CA); Carey Roth Bayer, Ed.D., R.N. (The Children’s Hospital of Philadelphia, Philadelphia, PA); Joseph Hess, R.N. (Penn State Children’s Hospital, Hershey, PA); Margaret Winkler, M.D. (The University of Alabama at Birmingham, Birmingham, AL); Robert Fitzgerald, M.D. (Devos Children’s Hospital, Grand Rapids, MI); Gwenn McLaughlin, M.D. (Jackson Memorial Hospital, Miami, FL); Cheri Landers, M.D. (Kentucky Children’s Hospital, Lexington, KY); Gary Kohn, M.D. (Morristown Memorial Hospital, Morristown, NJ); Paul Checchia, M.D. (St. Louis Children’s Hospital, St. Louis, MO); Jose Gutierrez, M.D. (Pediatric Critical Care of Arizona, Phoenix, AZ); Nick Anas, M.D. (Children’s Hospital of Orange County, Orange, CA) and Steve Shane, M.D. (Washoe Medical Center, Reno, NV). Supported by a grant from the National Institute of General Medical Sciences (RO1 GM064619), and The Amanda Kanowitz Foundation (http://www.amandakfoundation.org).
- 23.Malatack JJ, Blatt J, Penchansky L. (1997) Hematology and oncology. In: Zittelli BJ, Davis HW (eds.) Atlas of Pediatric Physical Diagnosis. Mosby, St. Louis. p. 305–41.Google Scholar