Open Access

Gene expression profiling predicts response to temozolomide in malignant gliomas

  • Authors:
    • Atsuo Yoshino
    • Akiyoshi Ogino
    • Kazunari Yachi
    • Takashi Ohta
    • Takao Fukushima
    • Takao Watanabe
    • Yoichi Katayama
    • Yutaka Okamoto
    • Norio Naruse
    • Emiko Sano
    • Kouhei Tsumoto
  • View Affiliations

  • Published online on: June 1, 2010     https://doi.org/10.3892/ijo_00000621
  • Pages: 1367-1377
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Abstract

Malignant gliomas are highly lethal neoplasms that cannot be cured with currently available therapies. Temozolomide (TMZ) is a recently introduced alkylating agent that has yielded significant benefits and become a key agent in the treatment of high-grade gliomas. However, its survival benefit remains unsatisfactory. Understanding the molecular basis of TMZ sensitivity/resistance is necessary for improving the treatment outcome by devising strategies that are able to circumvent primary drug resistance. We therefore combined the in vitro TMZ response with microarray gene expression data to identify genes that could potentially be used to predict the response of malignant gliomas to TMZ therapy. We first obtained the individual IC50 values for TMZ in seven malignant glioma cell lines (A-172, AM-38, T98G, U-87MG, U-138MG, U-251MG and YH-13) and then identified the genes whose expression correlated most highly with TMZ sensitivity employing a cDNA microarray. We present here a list of the most highly up-regulated and down-regulated genes which may be involved in conferring TMZ sensitivity/resistance in malignant gliomas, although most of the genes have not been implicated as a causal factor in the TMZ response except MGMT. We also demonstrated and confirmed the MGMT methylation status, quantitative MGMT mRNA levels, and MGMT protein expression levels in TMZ resistant glioma cells in vitro. Our results are thus consistent with previous studies and suggest that a dominant mechanism conferring sensitivity/resistance to TMZ exists in malignant glioma cells. Although the present study dose have several limitations, our reported candidate genes could represent not only potential molecular markers for TMZ sensitivity/resistance but also chemotherapy targets. Furthermore, the present study could provide a foundation for alternative therapeutic strategies including novel combination treatments that incorporate additional reagents directed at overcoming resistance to TMZ.

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June 2010
Volume 36 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yoshino A, Ogino A, Yachi K, Ohta T, Fukushima T, Watanabe T, Katayama Y, Okamoto Y, Naruse N, Sano E, Sano E, et al: Gene expression profiling predicts response to temozolomide in malignant gliomas. Int J Oncol 36: 1367-1377, 2010.
APA
Yoshino, A., Ogino, A., Yachi, K., Ohta, T., Fukushima, T., Watanabe, T. ... Tsumoto, K. (2010). Gene expression profiling predicts response to temozolomide in malignant gliomas. International Journal of Oncology, 36, 1367-1377. https://doi.org/10.3892/ijo_00000621
MLA
Yoshino, A., Ogino, A., Yachi, K., Ohta, T., Fukushima, T., Watanabe, T., Katayama, Y., Okamoto, Y., Naruse, N., Sano, E., Tsumoto, K."Gene expression profiling predicts response to temozolomide in malignant gliomas". International Journal of Oncology 36.6 (2010): 1367-1377.
Chicago
Yoshino, A., Ogino, A., Yachi, K., Ohta, T., Fukushima, T., Watanabe, T., Katayama, Y., Okamoto, Y., Naruse, N., Sano, E., Tsumoto, K."Gene expression profiling predicts response to temozolomide in malignant gliomas". International Journal of Oncology 36, no. 6 (2010): 1367-1377. https://doi.org/10.3892/ijo_00000621