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Article Open Access

GLI2 expression levels in radical nephrectomy specimens as a predictor of disease progression in patients with metastatic clear cell renal cell carcinoma following treatment with sunitinib

  • Authors:
    • Junya Furukawa
    • Hideaki Miyake
    • Masato Fujisawa
  • View Affiliations / Copyright

    Affiliations: Division of Urology, Kobe University Graduate School of Medicine, Kobe 650‑0017, Japan
    Copyright: © Furukawa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 186-192
    |
    Published online on: July 6, 2016
       https://doi.org/10.3892/mco.2016.950
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Abstract

The aim of the present study was to investigate the role of the Hedgehog signaling pathway in the progression of metastatic clear cell renal cell carcinoma (m-ccRCC) as well as the molecular targets of sunitinib, an inhibitor of multiple tyrosine kinases. A total of 39 patients subjected to radical nephrectomy who were diagnosed with m‑ccRCC and were subsequently treated with sunitinib were enrolled in the present study. The expression levels of the Hedgehog signaling proteins (GLI1, GLI2, cyclin D1, cyclin E and transforming growth factor‑β) and major molecular targets of sunitinib [vascular endothelial growth factor receptor (VEGFR)‑1 and ‑2, and platelet‑derived growth factor receptor‑α and ‑β] in primary RCC specimens were assessed by immunohistochemical staining. The expression levels of GLI2, VEGFR-1, VEGFR‑2 and pre‑treatment C‑reactive protein as well as the Memorial Sloan‑Kettering Cancer Center risk were identified as significant predictors of progression‑free survival (PFS). Of these, only GLI2 expression was independently correlated to PFS according to multivariate analysis. Furthermore, treatment with sunitinib resulted in a marked inhibition of GLI2 expression in the parental human RCC ACHN cell line, but not in ACHN cells with acquired resistance to sunitinib. These findings suggested that GLI2 may be involved in the acquisition of resistance to sunitinib in RCC; thus, it may be useful to consider the expression levels of GLI2 in addition to conventional prognostic parameters when selecting m-ccRCC patients likely to benefit from treatment with sunitinib.
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Copy and paste a formatted citation
Spandidos Publications style
Furukawa J, Miyake H and Fujisawa M: GLI2 expression levels in radical nephrectomy specimens as a predictor of disease progression in patients with metastatic clear cell renal cell carcinoma following treatment with sunitinib. Mol Clin Oncol 5: 186-192, 2016.
APA
Furukawa, J., Miyake, H., & Fujisawa, M. (2016). GLI2 expression levels in radical nephrectomy specimens as a predictor of disease progression in patients with metastatic clear cell renal cell carcinoma following treatment with sunitinib. Molecular and Clinical Oncology, 5, 186-192. https://doi.org/10.3892/mco.2016.950
MLA
Furukawa, J., Miyake, H., Fujisawa, M."GLI2 expression levels in radical nephrectomy specimens as a predictor of disease progression in patients with metastatic clear cell renal cell carcinoma following treatment with sunitinib". Molecular and Clinical Oncology 5.3 (2016): 186-192.
Chicago
Furukawa, J., Miyake, H., Fujisawa, M."GLI2 expression levels in radical nephrectomy specimens as a predictor of disease progression in patients with metastatic clear cell renal cell carcinoma following treatment with sunitinib". Molecular and Clinical Oncology 5, no. 3 (2016): 186-192. https://doi.org/10.3892/mco.2016.950
Copy and paste a formatted citation
x
Spandidos Publications style
Furukawa J, Miyake H and Fujisawa M: GLI2 expression levels in radical nephrectomy specimens as a predictor of disease progression in patients with metastatic clear cell renal cell carcinoma following treatment with sunitinib. Mol Clin Oncol 5: 186-192, 2016.
APA
Furukawa, J., Miyake, H., & Fujisawa, M. (2016). GLI2 expression levels in radical nephrectomy specimens as a predictor of disease progression in patients with metastatic clear cell renal cell carcinoma following treatment with sunitinib. Molecular and Clinical Oncology, 5, 186-192. https://doi.org/10.3892/mco.2016.950
MLA
Furukawa, J., Miyake, H., Fujisawa, M."GLI2 expression levels in radical nephrectomy specimens as a predictor of disease progression in patients with metastatic clear cell renal cell carcinoma following treatment with sunitinib". Molecular and Clinical Oncology 5.3 (2016): 186-192.
Chicago
Furukawa, J., Miyake, H., Fujisawa, M."GLI2 expression levels in radical nephrectomy specimens as a predictor of disease progression in patients with metastatic clear cell renal cell carcinoma following treatment with sunitinib". Molecular and Clinical Oncology 5, no. 3 (2016): 186-192. https://doi.org/10.3892/mco.2016.950
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