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Vol 45(2011) N 4 p. 600-607; U.A.Boyarskih1,2, Y.V. Kondrakhin4,5, I.S. Yevshin5,6, R.N. Sharipov5,6, A.M. Komelkov7, E.A. Musatkina7, E.M. Tchevkina7, M.A. Sukoyan2, F.A. Kolpakov4,5, K.N. Kashkin3, M.L. Filipenko1,2* Prediction of Nonsmall Cell Lung Cancer Sensitivity to Cisplastin and Paclitaxel Based on Marker Gene Expression 1Novosibirsk State University, Novosibirsk, 630090 Russia2Institute of Chemical biology and Fundamental Medicine of Siberian Branch of Russian Academy of Sciences, Novosibirsk, 630090 Russia 3Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow, 117997 Russia 4Design Technological Institute of Digital Techniques, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia 5Institute of System Biology, Novosibirsk, 630090 Russia 6Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090 Russia 7Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478 Russia *max@niboch.nsc.ru Received - 2010-10-22; Accepted - 2010-12-14 The goal of the present study was to define gene expression signatures that predict a chemosensitivity of nonsmall cell lung cancer (NSCLC) to cisplatin and paclitaxel. To generate a set of candidate genes likely to be predictive, current knowledge of the pathways involved in resistance and sensitivity to individual drugs was used. Forty-four genes coding proteins belonging to the 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, Calu1, 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 a high level of correlation (r = 0.91, p < 0.01). However, no model developed was able to reliably predict sensitivity of the NSCLC cells to cisplatin. nonsmall cell lung cancer, cisplatin, paclitaxel, resistance prediction, gene expression |
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