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Malignant Peritoneal Mesothelioma Interactome with 417 Novel Protein-Protein Interactions



Details

  • Personal Author:
  • Description:
    Background: Malignant peritoneal mesothelioma (MPeM) is an aggressive cancer affecting the abdominal peritoneal lining and intra-abdominal organs, with a median survival of approximately 2.5 years. Methods: We constructed the protein interactome of 59 MPeM-associated genes with previously known protein-protein interactions (PPIs) as well as novel PPIs predicted using our previously developed HiPPIP computational model and analysed it for transcriptomic and functional associations and for repurposable drugs. Results: The MPeM interactome had over 400 computationally predicted PPIs and 4700 known PPIs. Transcriptomic evidence validated 75.6% of the genes in the interactome and 65% of the novel interactors. Some genes had tissue-specific expression in extramedullary hematopoietic sites and the expression of some genes could be correlated with unfavourable prognoses in various cancers. 39 out of 152 drugs that target the proteins in the interactome were identified as potentially repurposable for MPeM, with 29 having evidence from prior clinical trials, animal models or cell lines for effectiveness against peritoneal and pleural mesothelioma and primary peritoneal cancer. Functional modules related to chromosomal segregation, transcriptional dysregulation, IL-6 production and hematopoiesis were identified from the interactome. The MPeM interactome overlapped significantly with the malignant pleural mesothelioma interactome, revealing shared molecular pathways. Conclusions: Our findings demonstrate the utility of the interactome in uncovering biological associations and in generating clinically translatable results. [Description provided by NIOSH]
  • Subjects:
  • Keywords:
  • ISSN:
    2731-9377
  • Document Type:
    Text
  • Funding:
    Cooperative Agreement
  • Genre:
    Journal Article
  • Place as Subject:
  • CIO:
    National Institute for Occupational Safety and Health (NIOSH)
  • Topic:
    Workplace Safety & Health
  • Location:
    North America
  • Pages in Document:
    42
  • Volume:
    2
  • NIOSHTIC Number:
    nn:20070300
  • Citation:
    BJC Rep 2024 May; 2:42
  • Contact Point Address:
    Madhavi K. Ganapathiraju, Department of Biomedical Informatics, School of Medicine, and Intelligent Systems Program, School of Computing and Information, University of Pittsburgh, 5607 Baum Blvd, 5th Floor, Pittsburgh, PA, 15206, USA
  • Email:
    madhavi@pitt.edu
  • Federal Fiscal Year:
    2024
  • NORA Priority Area:
  • Performing Organization:
    University of Pittsburgh at Pittsburgh
  • Peer Reviewed:
    True
  • Start Date:
    20060901
  • Source Full Name:
    BJC Reports
  • End Date:
    20260831
  • Collection(s):
  • Main Document Checksum:
    urn:sha-512:3b7a53750db649c88a6c660c68a7d3620f8ca509a07ce6e8211a07889491545ffdc247bd114ccc333c53a3ac87ee983a7d1e23f87c5cf7b36922171c5cc0f600
  • Download URL:
  • File Type:
    Filetype[PDF - 836.86 KB ]
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