title: Biased random walk model for the prioritization of drug resistance associated proteins.
abstract: Multi-drug resistance is the main cause of treatment failure in cancer patients. How to identify molecules underlying drug resistance from multi-omics data remains a great challenge. Here, we introduce a data biased strategy, ProteinRank, to prioritize drug-resistance associated proteins in cancer cells. First, we identified differentially expressed proteins in Adriamycin and Vincristine resistant gastric cancer cells compared to their parental cells using iTRAQ combined with LC-MS/MS experiments, and then mapped them to human protein-protein interaction network; second, we applied ProteinRank to analyze the whole network and rank proteins similar to known drug resistance related proteins. Cross validations demonstrated a better performance of ProteinRank compared to the method without usage of MS data. Further validations confirmed the altered expressions or activities of several top ranked proteins. Functional study showed PIM3 or CAV1 silencing was sufficient to reverse the drug resistance phenotype. These results indicated ProteinRank could prioritize key proteins related to drug resistance in gastric cancer and provided important clues for cancer research.
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, P. R. China.|State Key Laboratory of Proteomics, Beijing Proteome Research Centre, Beijing Institute of radiation Medicine, Beijing, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Sijun
authors.initials: S
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Guangbo
authors.initials: G
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Dou
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Tian
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Centre, Beijing Institute of radiation Medicine, Beijing, P. R. China.
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, P. R. China.
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D020543:Proteome; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism
chemical_list: D020543:Proteome