Dataset Information

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.

SUBMITTER: Huang CH

PROVIDER: S-EPMC4156989 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Drug repositioning discovery for early- and late-stage non-small-cell lung cancer.

Huang Chien-Hung CH Chang Peter Mu-Hsin PM Lin Yong-Jie YJ Wang Cheng-Hsu CH Huang Chi-Ying F CY Ng Ka-Lok KL

BioMed research international 20140818

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-spe ...[more]

PMID: 25210704

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Project description:Lung cancer is the most common cancer in men and women. This cancer is divided into two main types, namely non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Around 85 to 90 percent of lung cancers are NSCLC. Repositioning potent candidate drugs in NSCLC treatment is one of the important topics in cancer studies. Drug repositioning (DR) or drug repurposing is a method for identifying new therapeutic uses of existing drugs. The current study applies a computational drug repositioning method to identify candidate drugs to treat NSCLC patients. To this end, at first, the transcriptomics profile of NSCLC and healthy (control) samples was obtained from the GEO database with the accession number GSE21933. Then, the gene co-expression network was reconstructed for NSCLC samples using the WGCNA, and two significant purple and magenta gene modules were extracted. Next, a list of transcription factor genes that regulate purple and magenta modules' genes was extracted from the TRRUST V2.0 online database, and the TF-TG (transcription factors-target genes) network was drawn. Afterward, a list of drugs targeting TF-TG genes was obtained from the DGIdb V4.0 database, and two drug-gene interaction networks, including drug-TG and drug-TF, were drawn. After analyzing gene co-expression TF-TG, and drug-gene interaction networks, 16 drugs were selected as potent candidates for NSCLC treatment. Out of 16 selected drugs, nine drugs, namely Methotrexate, Olanzapine, Haloperidol, Fluorouracil, Nifedipine, Paclitaxel, Verapamil, Dexamethasone, and Docetaxel, were chosen from the drug-TG sub-network. In addition, nine drugs, including Cisplatin, Daunorubicin, Dexamethasone, Methotrexate, Hydrocortisone, Doxorubicin, Azacitidine, Vorinostat, and Doxorubicin Hydrochloride, were selected from the drug-TF sub-network. Methotrexate and Dexamethasone are common in drug-TG and drug-TF sub-networks. In conclusion, this study proposed 16 drugs as potent candidates for NSCLC treatment through analyzing gene co-expression, TF-TG, and drug-gene interaction networks.

Dataset Information

Drug repositioning discovery for early- and late-stage non-small-cell lung cancer.

Publications

Drug repositioning discovery for early- and late-stage non-small-cell lung cancer.

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