Project name: Homo sapiens

Description: 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 PC9GSM94304 PC7GSM94305 PC14GSM94306 A549GSM94308 LK2GSM94313 RERF LC-KJGSM94314 RERF LC-MSGSM94315 RERF-LC-AIGSM94316 PC-1GSM94317 PC-3GSM94319 PC-10GSM94323 ABC-1GSM94324 EBC-1GSM94325 LC2/adGSM94328 SQ-5GSM94329 QG-56test sample set:GSM94307 LU65GSM94326 LC1/sqGSM94327 LC-1FGSM254967 LCOKGSM254968 LCDGSM254969 H1650GSM254970 H1975Keywords: HDAC inhibitor, NSCLC, cDNA array, drug sensitivity test, pathway analysisOverall design: gene expression analyis in lung cancer cell lines

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: Medical

Release date: 2008-01-08

Last updated: 2008-01-07