Integrative network analysis identifies potential targets and drugs for ovarian cancer
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RESEARCH
Open Access
Integrative network analysis identifies potential targets and drugs for ovarian cancer Tianyu Zhang1,2, Liwei Zhang2 and Fuhai Li1,3* From The International Conference on Intelligent Biology and Medicine (ICIBM) 2019 Columbus, OH, USA. 9-11 June 2019
Abstract Background: Though accounts for 2.5% of all cancers in female, the death rate of ovarian cancer is high, which is the fifth leading cause of cancer death (5% of all cancer death) in female. The 5-year survival rate of ovarian cancer is less than 50%. The oncogenic molecular signaling of ovarian cancer are complicated and remain unclear, and there is a lack of effective targeted therapies for ovarian cancer treatment. Methods: In this study, we propose to investigate activated signaling pathways of individual ovarian cancer patients and sub-groups; and identify potential targets and drugs that are able to disrupt the activated signaling pathways. Specifically, we first identify the up-regulated genes of individual cancer patients using Markov chain Monte Carlo (MCMC), and then identify the potential activated transcription factors. After dividing ovarian cancer patients into several sub-groups sharing common transcription factors using K-modes method, we uncover the upstream signaling pathways of activated transcription factors in each sub-group. Finally, we mapped all FDA approved drugs targeting on the upstream signaling. Results: The 427 ovarian cancer samples were divided into 3 sub-groups (with 100, 172, 155 samples respectively) based on the activated TFs (with 14, 25, 26 activated TFs respectively). Multiple up-stream signaling pathways, e.g., MYC, WNT, PDGFRA (RTK), PI3K, AKT TP53, and MTOR, are uncovered to activate the discovered TFs. In addition, 66 FDA approved drugs were identified targeting on the uncovered core signaling pathways. Forty-four drugs had been reported in ovarian cancer related reports. The signaling diversity and heterogeneity can be potential therapeutic targets for drug combination discovery. Conclusions: The proposed integrative network analysis could uncover potential core signaling pathways, targets and drugs for ovarian cancer treatment. Keywords: Ovarian cancer, Core signaling pathways, Network analysis, Drug discovery
* Correspondence: [email protected] 1 Institute for Informatics (I2), Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO 63130, USA 3 Department of Pediatrics, Washington University School of Medicine, Washington University in St. Louis, St. Louis, MO 63130, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party materia
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