RESUMEN
The goal of the present study was to define gene expression signatures that predict a chemosensitivity of non-small cell lung cancer (NSCLC) to cisplatin and paclitaxel. To generate set of candidate genes likely to be predictive a current knowledge of the pathways involved in resistance and sensitivity to individual drugs was used. Forty four genes coding proteins belonging to following categories: ATP-dependent transport proteins, detoxification system proteins, reparation system proteins, tubulin and proteins responsible for its synthesis, cell cycle and apoptosis proteins were considered. Eight NSCLC cell lines (A549, Calul, H1299, H322, H358, H460, H292, and H23) were used in our study. For each NSCLC cell line a cisplatin and paclitaxel chemosensitivity as well as an expression level of 44 candidate genes were evaluated. To develop a chemosensitivity prediction model based on selected genes expression level a multiple regression analysis was performed. The model based on the expression level of 11 genes (TUBB3, TXR1, MRP5, MSH2, ERCC1, STMN, SMAC, FOLR1, PTPN14, HSPA2, GSTP1) allowed us to predict the paclitaxel cytotoxic concentration with high level of correlation (r = 0.91, p < 0.01). However, none model developed was able to reliably predict a sensitivity of the NSCLC cells to cisplatin.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos/genética , Neoplasias Pulmonares/tratamiento farmacológico , Paclitaxel/uso terapéutico , Línea Celular Tumoral , Expresión Génica , Humanos , PronósticoRESUMEN
We have developed GeneExpress that is the WWW-oriented integrator for the databases and systems supporting the investigation of gene expression. The total number of the Web-based resources integrated is 30. The database GeneNet on molecular events forming gene networks was assigned its integrative core. To navigate all these WWW-available resources, the SRS, HTML, and Java viewers were developed, http:@wwwmgs.bionet.nsc.ru/systems/GeneExpress/.
Asunto(s)
Sistemas de Administración de Bases de Datos , Expresión Génica , Internet , Integración de Sistemas , Lenguajes de ProgramaciónAsunto(s)
Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas de Unión al ADN/genética , Factor de Transcripción AP-1/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Proteínas de Unión al ADN/metabolismo , Factores de Unión a la G-Box , Datos de Secuencia Molecular , Factores de Transcripción/metabolismoRESUMEN
Using a set of sequences of 63 cleavage/polyadenylation sites of vertebrate pre-mRNA, a generalized consensus matrix was constructed. The elements of the matrix were the absolute frequencies of oligonucleotides of length l at the i-th position of the sites (the cleavage point of each site was assigned the same position number). To recognize a polyadenylation site in a nucleotide sequence, a multiplicative measure was obtained using the elements of the generalized consensus matrix as weighting factors. For any omega-long fragment of a nucleotide sequence, the estimated value of the functional mu was compared with the threshold value mu. Based on the results obtained, we determined whether or not the given fragment is a processing site.