Transcriptomics

Dataset Information

40

Transcription profiling of human NSCLC cell lines treated with Trichostatin A and vorinostat to test Anti-tumor Activity of Histone Deacetylase Inhibitors


ABSTRACT: In order to ascertain the potential for histone deacetylase (HDAC) inhibitor-based treatment in non-small cell lung cancer (NSCLC), we analyzed the anti-tumour effects of Trichostatin A (TSA) and suberoylanilide hydroxamic acid (vorinostat) in a panel of 16 NSCLC cell lines via MTT assay. TSA and vorinostat both displayed strong anti-tumor activities in a proportion of NSCLC cell lines, and suggesting the need for the use of predictive markers to select patients receiving this treatment. There was a strong correlation between the responsiveness to TSA and vorinostat (P < 0.0001). To identify a molecular model of sensitivity to HDAC inhibitor treatment in NSCLC, we conducted a gene expression profiling study using cDNA arrays on the same set of cell lines and related the cytotoxic activity of TSA to corresponding gene expression pattern using a modified NCI program. In addition, pathway analysis was performed with Pathway Architect software. We used nine genes, which were identified by gene-drug sensitivity correlation and pathway analysis, to build a support vector machine (SVM) algorithm model by which sensitive cell lines were distinguished from resistant cell lines. The prediction performance of the SVM model was validated by an additional seven cell lines, resulting in a prediction value of 100% in respect to determining response to TSA. Our results suggested that [1] HDAC inhibitors may be promising anticancer drugs to NSCLC, and [2] the nine gene classifer is useful in predicting drug sensitivity to HDAC inhibitors and may contribute to achieving individualized therapy for NSCLC patients. training sample set:; GSM94303 PC9; GSM94304 PC7; GSM94305 PC14; GSM94306 A549; GSM94308 LK2; GSM94313 RERF LC-KJ; GSM94314 RERF LC-MS; GSM94315 RERF-LC-AI; GSM94316 PC-1; GSM94317 PC-3; GSM94319 PC-10; GSM94323 ABC-1; GSM94324 EBC-1; GSM94325 LC2/ad; GSM94328 SQ-5; GSM94329 QG-56; test sample set:; GSM94307 LU65; GSM94326 LC1/sq; GSM94327 LC-1F; GSM254967 LCOK; GSM254968 LCD; GSM254969 H1650; GSM254970 H1975 Experiment Overall Design: gene expression analyis in lung cancer cell lines

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Homo sapiens  

SUBMITTER: Akihiko Gemma  

PROVIDER: E-GEOD-10089 | ArrayExpress | 2011-10-12

SECONDARY ACCESSION(S): GSE10089PRJNA108655

REPOSITORIES: GEO, ArrayExpress

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