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Prediction of nonsmall cell lung cancer sensitivity to cisplastin and paclitaxel based on marker gene expression

  • Molecular Biology of the Cell
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Abstract

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.

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Abbreviations

MDR:

multiple drug resistance

NSCLC:

nonsmall cell lung cancer

References

  1. Velichko S.A., Miller S.V., Tuzikov S.A., et al. 2008. Spiral computer tomography in assessing the efficiency of neoadjuvant treatment of non-small-cell ling cancer. Sib. Onkol. Zh. 3, 66–69.

    Google Scholar 

  2. Wan H., Williams R., Doherty P., Williams D.F. 1994. A study of the reproducibility of the MTT test. J. Mater. Sci: Mater. Med. 5, 154–159.

    Article  Google Scholar 

  3. Kavallaris M., Kuo D.Y., Burkhart C.A., et al. 1997. Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J. Clin. Invest. 100, 1282–1293.

    Article  PubMed  CAS  Google Scholar 

  4. Curmi P.A., Andersen S.S., Lachkar S., et al. 1997. The stathmin/tubulin interaction in vitro. J. Biol. Chem. 272, 25029–25036.

    Article  PubMed  CAS  Google Scholar 

  5. Chih-Jian Lih, Wensheng Wei, Cohen S.N. 2006. Txr1: A transcriptional regulator of thrombospondin-1 that modulates cellular sensitivity to taxanes. Genes Dev. 20, 2082–2095.

    Article  Google Scholar 

  6. Rosell R., Lord R.V., Taron M., Reguart N. 2002. DNA repair and cisplatin resistance in non-small-cell lung cancer. Lung Cancer. 38, 217–227.

    Article  PubMed  Google Scholar 

  7. Ferry K.V., Hamilton T.C., Johnson S.W. 2000. Increased nucleotide excision repair in cisplatin-resistant ovarian cancer cells: Role of ercc1-xpf. Biochem. Pharmacol. 60, 1305–1313.

    Article  PubMed  CAS  Google Scholar 

  8. Gan Wang, Lynn Chuang, Xiaohong Zhang, et al. 2004. The initiative role of XPC protein in cisplatin DNA damaging treatment-mediated cell cycle regulation. Nucleic Acids Res. 32, 2231–2240.

    Article  Google Scholar 

  9. Topping R.P., Wilkinson J.C., Scarpinato K.D. 2009. Mismatch repair protein deficiency compromises cisplatin-induced apoptotic signaling. J. Biol. Chem. 284, 14029–14039.

    Article  PubMed  CAS  Google Scholar 

  10. Takayuki Torigoe, Hiroto Izumi, Hiroshi Ishiguchi, et al. Cisplatin resistance and transcription factors. Curr. Med. Chem. 5, 15–27.

  11. Biaglow J.E., Miller R.A. 2005. The thioredoxin reductase/thioredoxin system: Novel redox targets for cancer therapy. Cancer Biol. Ther. 4, 6–13.

    Article  PubMed  CAS  Google Scholar 

  12. Penning T.M. 2005. AKR1B10: A new diagnostic marker of non-small cell lung carcinoma in smokers. Clin. Cancer Res. 11, 1687–1690.

    Article  PubMed  CAS  Google Scholar 

  13. Szakács G., Paterson J.K., Ludwig J.A., Booth-Genthe C., Gottesman M.M. 2006. Targeting multidrug resistance in cancer. Nature Rev. Drug Discov. 5, 219–234.

    Article  Google Scholar 

  14. Sheps J.A., Ling V. 2007. Preface: The concept and consequences of multidrug resistance. Eur. J. Physiol. 453, 545–553.

    Article  CAS  Google Scholar 

  15. Ying Huanga, Anderle P., Sadéeb W., et al. 2004. Membrane transporters and channels: Role of the transportome in cancer chemosensitivity and chemoresistance. Cancer Res. 64, 4294–4301.

    Article  Google Scholar 

  16. Townsend D.M., Tew K.D. 2003. The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene. 22, 7369–7375.

    Article  PubMed  CAS  Google Scholar 

  17. Pommier Y., Sordet O., Antony S., et al. 2004. Apoptosis defects and chemotherapy resistance: Molecular interaction maps and networks. Oncogene. 23, 2934–2949.

    Article  PubMed  CAS  Google Scholar 

  18. Herr I., Debatin K. 2001. Cellular stress response and apoptosis in cancer therapy. Blood. 98, 2603–2614.

    Article  PubMed  CAS  Google Scholar 

  19. Vayshlya N.A., Zinovyeva M.V., Sass A.V., Kopantzev E.P., Vinogradova T.V, Sverdlov E.D. 2008. Increased expression of BIRC5 in non-small cell lung cancer and esophageal squamous cell carcinoma does not correlate with the expression of its inhibitors SMAC/DIABLO and PML. Mol. Biol. (Moscow). 42, 579–587.

    Article  CAS  Google Scholar 

  20. Scieglin-ska D., Pigłowski W., Mazurek A., et al. 2008. The HspA2 protein localizes in nucleoli and centrosomes of heat shocked cancer cells. J. Cell. Biochem. 104, 2193–2206.

    Article  CAS  Google Scholar 

  21. Hynes N.E., MacDonald G. 2009. ErbB receptors and signaling pathways in cancer. Curr. Opin. Cell Biol. 21, 177–184.

    Article  PubMed  CAS  Google Scholar 

  22. Wadham C., Gamble J.R., Vadas M.A., Khew-Goodall Y. 2003. The protein tyrosine phosphatase Pez is a major phosphatase of adherens junctions and dephosphorylates β-catenin. Mol. Biol. Cell. 14, 2520–2529.

    Article  PubMed  CAS  Google Scholar 

  23. Pupa S.M., Giuffre S., Castiglioni F., et al. 2007. Regulation of breast cancer response to chemotherapy by Fibulin-1. Cancer Res. 67, 4271–4277.

    Article  PubMed  CAS  Google Scholar 

  24. Chao-Chi Hoab, Sung-Hsin Kuoc, Pei-Hsin Huangd, et al. 2008. Caveolin-1 expression is significantly associated with drug resistance and poor prognosis in advanced non-small cell lung cancer patients treated with gemcitabine-based chemotherapy. Lung Cancer. 59, 105–110.

    Article  Google Scholar 

  25. Goetz J.G., Lajoie P., Wiseman S.M., Nabi I.R. 2008. Caveolin-1 in tumor progression: The good, the bad and the ugly. Cancer Metastasis Rev. 27, 715–735.

    Article  PubMed  CAS  Google Scholar 

  26. Shin-ichi Fukumoto, Naoko Yamauchi, Hisashi Moriguchi, et al. 2005. Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers’ non-small cell lung carcinomas. Clin. Cancer Res. 11, 1776–1785.

    Article  PubMed  CAS  Google Scholar 

  27. Hirotaka Osada, Yoshio Tatematsu, Yasushi Yatabe, et al. 2002. Frequent and histological type-specific inactivation of 14-3-3sigma in human lung cancers. Oncogene. 21, 2418–2424.

    Article  PubMed  CAS  Google Scholar 

  28. Cohen S.M., Lippard S.J. 2001. Cisplatin: From DNA damage to cancer chemotherapy. Prog. Nucleic Acid Res. Mol. Biol. 67, 93–130.

    Article  PubMed  CAS  Google Scholar 

  29. Zejia Yang, Schumaker L.M., Egorin M.J., et al. 2006. Cisplatin preferentially binds mitochondrial DNA and voltage-dependent anion channel protein in the mitochondrial membrane of head and neck squamous cell carcinoma: Possible role in apoptosis. Clin. Cancer Res. 12, 5817–5825.

    Article  PubMed  CAS  Google Scholar 

  30. Martins N.M., Santos N.A., Curti C., et al. 2008. Cisplatin induces mitochondrial oxidative stress with resultant energetic metabolism impairment, membrane rigidification and apoptosis in rat liver. J. Appl. Toxicol. 28, 337–344.

    Article  PubMed  CAS  Google Scholar 

  31. Shchepetkin I.A., Plotnikov V.M., Kagiya V.T. 2001. Effect of platinum derivatives on the activity of microsomal NADPH-oxidoreductases. Vopr. Med. Khim. 47, 1–5.

    Google Scholar 

  32. Derry W.B., Wilson L., Khan I.A., et al. 1997. Taxol differentially modulates the dynamics of microtubules assembled from unfractionated and purified beta-tubulin isotypes. Biochemistry. 36, 3554–3562.

    Article  PubMed  CAS  Google Scholar 

  33. Bhalla K.N. 2003. Microtubule-targeted anticancer agents and apoptosis. Oncogene. 22, 9075–9086.

    Article  PubMed  CAS  Google Scholar 

  34. Potti A., Dressman H.K., Bild A., et al. 2006. Genomic signatures to guide the use of chemotherapeutics. Nature Med. 12, 1294–1300.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    U. A. Boyarskikh, M. A. Sukoyan & M. L. Filipenko

  2. Novosibirsk State University, Novosibirsk, 630090, Russia

    U. A. Boyarskikh & M. L. Filipenko

  3. Institute of System Biology, Novosibirsk, 630090, Russia

    Yu. V. Kondrakhin, I. S. Yevshin, R. N. Sharipov & F. A. Kolpakov

  4. Design Technological Institute of Digital Techniques, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    Yu. V. Kondrakhin & F. A. Kolpakov

  5. Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090, Russia

    I. S. Yevshin & R. N. Sharipov

  6. Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Moscow, 115478, Russia

    A. V. Komelkov, E. A. Musatkina & E. M. Tchevkina

  7. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia

    K. N. Kashkin

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  1. U. A. Boyarskikh
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  2. Yu. V. Kondrakhin
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  3. I. S. Yevshin
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  6. E. A. Musatkina
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  7. E. M. Tchevkina
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  8. M. A. Sukoyan
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  9. F. A. Kolpakov
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Correspondence to U. A. Boyarskikh.

Additional information

Original Russian Text © U.A. Boyarskikh, Yu.V. Kondrakhin, I.S. Yevshin, R.N. Sharipov, A.V. Komelkov, E.A. Musatkina, E.M. Tchevkina, M.A. Sukoyan, F.A. Kolpakov, K.N. Kashkin, M.L. Filipenko, 2011, published in Molekulyarnaya Biologiya, 2011, Vol. 45, No. 4, pp. 652–661.

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Boyarskikh, U.A., Kondrakhin, Y.V., Yevshin, I.S. et al. Prediction of nonsmall cell lung cancer sensitivity to cisplastin and paclitaxel based on marker gene expression. Mol Biol 45, 600–607 (2011). https://doi.org/10.1134/S0026893311030034

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  • DOI: https://doi.org/10.1134/S0026893311030034

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