title: Identification of Genes Associated with Breast Cancer Metastasis to Bone on a Protein-Protein Interaction Network with a Shortest Path Algorithm.
abstract: Tumor metastasis is defined as the spread of tumor cells from one organ or part to another that is not directly connected to it, which significantly contributes to the progression and aggravation of tumorigenesis. Because it always involves multiple organs, the metastatic process is difficult to study in its entirety. Complete identification of the genes related to this process is an alternative way to study metastasis. In this study, we developed a computational method to identify such genes. To test our method, we selected breast cancer bone metastasis. A large network was constructed using human protein-protein interactions. On the basis of the validated genes related to breast and bone cancer, a shortest path algorithm was applied to the network to search for novel genes that may mediate breast cancer metastasis to bone. In addition, further rules constructed using the permutation FDR, the betweenness ratio, and the max-min interaction score were also employed in the method to make the inferred genes more reliable. Eighteen putative genes were identified by the method and were extensively analyzed. The confirmation results indicate that these genes participate in metastasis.
authors.affiliation: School of Life Sciences, Shanghai University , Shanghai 200444 People's Republic of China.
authors.forename: Yu-Dong
authors.initials: YD
authors.lastname: Cai
authors.affiliation: School of Life Sciences, Shanghai University , Shanghai 200444 People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, People's Republic of China.
authors.forename: Yu-Hang
authors.initials: YH
authors.lastname: Zhang
authors.affiliation: College of Information Engineering, Shanghai Maritime University , Shanghai 201306, People's Republic of China.
authors.forename: Lei
authors.identifier: 0000-0003-3068-1583
authors.initials: L
authors.lastname: Chen
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences , Shanghai 200031, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Huang
mesh_terms: D000465:Algorithms; D001859:Bone Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000556:secondary; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D025941:Protein Interaction Mapping / Q000379:methods*
chemical_list: D009363:Neoplasm Proteins
keywords: bone cancer; breast cancer; breast cancer metastasis to bone; protein−protein interaction; shortest path algorithm