J Christopher States1, Ming Ouyang2, C William Helm3. 1. Department of Pharmacology & Toxicology, University of Louisville, Louisville, KY, USA. Electronic address: jcstates@louisville.edu. 2. Department of Computer Engineering & Computer Science, University of Louisville, Louisville, KY, USA. 3. Department of Obstetrics, Gynecology & Women's Health, Saint Louis University, St. Louis, MO, USA.
Abstract
BACKGROUND: The most effective way to reduce cancer burden is Q2 prevention which is dependent on identifying individuals at risk for a particular cancer and counseling them to avoid exposure to causative agents. Other than a few well characterized environmental agents linked to specific cancers, linkage between any particular environmental exposure and a specific type of cancer is mostly unknown. Thus, we propose a systems approach to analyze publicly available large datasets to identify candidate agents that play a role in organ-specific carcinogenesis. METHODS: Publicly available datasets for mRNA and miRNA expression in ovarian cancer were queried to define the differentially expressed genes that are also targets of differentially expressed miRNAs. These target genes were then used to query the Comparative Toxicogenomics Database to identify interacting chemicals and also were analyzed by Ingenuity Pathway Analysis to identify pathways. RESULTS: The interacting chemicals interact with genes in known pathways in ovarian carcinogenesis and support the hypothesis that these chemicals are likely etiologic agents in ovarian carcinogenesis. CONCLUSION: A systems approach may prove useful to identify specific etiologic agents to better develop personalized preventive medicine strategies for those most at risk.
BACKGROUND: The most effective way to reduce cancer burden is Q2 prevention which is dependent on identifying individuals at risk for a particular cancer and counseling them to avoid exposure to causative agents. Other than a few well characterized environmental agents linked to specific cancers, linkage between any particular environmental exposure and a specific type of cancer is mostly unknown. Thus, we propose a systems approach to analyze publicly available large datasets to identify candidate agents that play a role in organ-specific carcinogenesis. METHODS: Publicly available datasets for mRNA and miRNA expression in ovarian cancer were queried to define the differentially expressed genes that are also targets of differentially expressed miRNAs. These target genes were then used to query the Comparative Toxicogenomics Database to identify interacting chemicals and also were analyzed by Ingenuity Pathway Analysis to identify pathways. RESULTS: The interacting chemicals interact with genes in known pathways in ovarian carcinogenesis and support the hypothesis that these chemicals are likely etiologic agents in ovarian carcinogenesis. CONCLUSION: A systems approach may prove useful to identify specific etiologic agents to better develop personalized preventive medicine strategies for those most at risk.
Authors: Stacia K Wyman; Rachael K Parkin; Patrick S Mitchell; Brian R Fritz; Kathy O'Briant; Andrew K Godwin; Nicole Urban; Charles W Drescher; Beatrice S Knudsen; Muneesh Tewari Journal: PLoS One Date: 2009-04-23 Impact factor: 3.240
Authors: Jiguo Wu; Ana P Ferragut Cardoso; Vanessa A R States; Laila Al-Eryani; Mark Doll; Sandra S Wise; Shesh N Rai; J Christopher States Journal: Toxicol Appl Pharmacol Date: 2019-06-06 Impact factor: 4.219