A systems biology approach to the study of cisplatin drug resistance in ovarian cancers

Jake Y. Chen, Zhong Yan, Changyu Shen, Dawn P G Fitzpatrick, Mu Wang

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Cisplatin-induced drug resistance is known to involve a complex set of cellular changes whose molecular mechanism details remain unclear. In this study, we developed a systems biology approach to examine proteomics- and network-level changes between cisplatin-resistant and cisplatin-sensitive cell lines. This approach involves experimental investigation of differential proteomics profiles and computational study of activated enriched proteins, protein interactions, and protein interaction networks. Our experimental platform is based on a Label-free liquid Chromatography/mass spectrometry proteomics platform. Our computational methods start with an initial list of 119 differentially expressed proteins. We expanded these proteins into a cisplatin-resistant activated sub-network using a database of human protein-protein interactions. An examination of network topology features revealed the activated responses in the network are closely coupled. By examining sub-network proteins using gene ontology categories, we found significant enrichment of proton-transporting ATPase and ATP synthase complexes activities in cisplatin-resistant cells in the form of cooperative down-regulations. Using two-dimensional visualization matrixes, we further found significant cascading of endogenous, abiotic, and stress-related signals. Using a visual representation of activated protein categorical sub-networks, we showed that molecular regulation of cell differentiation and development caused by responses to proteome-wide stress as a key signature to the acquired drug resistance.

Original languageEnglish
Pages (from-to)383-405
Number of pages23
JournalJournal of Bioinformatics and Computational Biology
Volume5
Issue number2 A
StatePublished - Apr 2007

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Systems Biology
Drug Resistance
Ovarian Neoplasms
Cisplatin
Proteins
Pharmaceutical Preparations
Proteomics
Protein Interaction Maps
Protein Databases
Gene Ontology
Cells
Proteome
Liquid Chromatography
Adenosine Triphosphatases
Protons
Liquid chromatography
Cell Differentiation
Mass Spectrometry
Computational methods
Adenosinetriphosphate

Keywords

  • Gene ontology
  • Ovarian cancer
  • Protein interaction network
  • Proteomics
  • Systems biology
  • Visualization

ASJC Scopus subject areas

  • Medicine(all)
  • Cell Biology

Cite this

A systems biology approach to the study of cisplatin drug resistance in ovarian cancers. / Chen, Jake Y.; Yan, Zhong; Shen, Changyu; Fitzpatrick, Dawn P G; Wang, Mu.

In: Journal of Bioinformatics and Computational Biology, Vol. 5, No. 2 A, 04.2007, p. 383-405.

Research output: Contribution to journalArticle

Chen, Jake Y. ; Yan, Zhong ; Shen, Changyu ; Fitzpatrick, Dawn P G ; Wang, Mu. / A systems biology approach to the study of cisplatin drug resistance in ovarian cancers. In: Journal of Bioinformatics and Computational Biology. 2007 ; Vol. 5, No. 2 A. pp. 383-405.
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