title: Drug repositioning discovery for early- and late-stage non-small-cell lung cancer.
abstract: Drug repositioning is a popular approach in the pharmaceutical industry for identifying potential new uses for existing drugs and accelerating the development time. Non-small-cell lung cancer (NSCLC) is one of the leading causes of death worldwide. To reduce the biological heterogeneity effects among different individuals, both normal and cancer tissues were taken from the same patient, hence allowing pairwise testing. By comparing early- and late-stage cancer patients, we can identify stage-specific NSCLC genes. Differentially expressed genes are clustered separately to form up- and downregulated communities that are used as queries to perform enrichment analysis. The results suggest that pathways for early- and late-stage cancers are different. Sets of up- and downregulated genes were submitted to the cMap web resource to identify potential drugs. To achieve high confidence drug prediction, multiple microarray experimental results were merged by performing meta-analysis. The results of a few drug findings are supported by MTT assay or clonogenic assay data. In conclusion, we have been able to assess the potential existing drugs to identify novel anticancer drugs, which may be helpful in drug repositioning discovery for NSCLC.
authors.affiliation: Department of Computer Science and Information Engineering, National Formosa University, 64 Wen-Hwa Road, Hu-Wei, Yun-Lin 632, Taiwan.
authors.forename: Chien-Hung
authors.identifier: 0000-0003-3905-8915
authors.initials: CH
authors.lastname: Huang
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Faculty of Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Peter Mu-Hsin
authors.initials: PM
authors.lastname: Chang
authors.affiliation: Department of Computer Science and Information Engineering, National Formosa University, 64 Wen-Hwa Road, Hu-Wei, Yun-Lin 632, Taiwan.
authors.forename: Yong-Jie
authors.initials: YJ
authors.lastname: Lin
authors.affiliation: Cancer Center, Keelung Chang Gang Memorial Hospital, Keelung 204, Taiwan.
authors.forename: Cheng-Hsu
authors.initials: CH
authors.lastname: Wang
authors.affiliation: Institute of Biopharmaceutical Sciences, National Yang-Ming University, No. 155, Section 2, Linong Street, Taipei 112, Taiwan ; Genome Research Center, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Chi-Ying F
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Biomedical Informatics, Asia University, 500 Lioufeng Road, Wufeng Shiang, Taichung 41354, Taiwan ; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan.
authors.forename: Ka-Lok
authors.identifier: 0000-0001-6315-6326
authors.initials: KL
authors.lastname: Ng
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D055808:Drug Discovery; D058492:Drug Repositioning; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D046228:Microarray Analysis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009367:Neoplasm Staging; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins