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Myopodin methylation is a prognostic biomarker and predicts antiangiogenic response in advanced kidney cancer

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Tumor Biology

Abstract

Myopodin is a cytoskeleton protein that shuttles to the nucleus depending on the cellular differentiation and stress. It has shown tumor suppressor functions. Myopodin methylation status was useful for staging bladder and colon tumors and predicting clinical outcome. To our knowledge, myopodin has not been tested in kidney cancer to date. The purpose of this study was to evaluate whether myopodin methylation status could be clinically useful in renal cancer (1) as a prognostic biomarker and 2) as a predictive factor of response to antiangiogenic therapy in patients with metastatic disease. Methylation-specific polymerase chain reactions (MS-PCR) were used to evaluate myopodin methylation in 88 kidney tumors. These belonged to patients with localized disease and no evidence of disease during follow-up (n = 25) (group 1), and 63 patients under antiangiogenic therapy (sunitinib, sorafenib, pazopanib, and temsirolimus), from which group 2 had non-metastatic disease at diagnosis (n = 32), and group 3 showed metastatic disease at diagnosis (n = 31). Univariate and multivariate Cox analyses were utilized to assess outcome and response to antiangiogenic agents taking progression, disease-specific survival, and overall survival as clinical endpoints. Myopodin was methylated in 50 out of the 88 kidney tumors (56.8 %). Among the 88 cases analyzed, 10 of them recurred (11.4 %), 51 progressed (57.9 %), and 40 died of disease (45.4 %). Myopodin methylation status correlated to MSKCC Risk score (p = 0.050) and the presence of distant metastasis (p = 0.039). Taking all patients, an unmethylated myopodin identified patients with shorter progression-free survival, disease-specific survival, and overall survival. Using also in univariate and multivariate models, an unmethylated myopodin predicted response to antiangiogenic therapy (groups 2 and 3) using progression-free survival, disease-specific, and overall survival as clinical endpoints. Myopodin was revealed hypermethylated in kidney cancer. Myopodin methylation status identified which patients showed a more aggressive clinical behavior and predicted antiangiogenic response. These observations support the clinical utility of an unmethylated myopodin as a prognostic and predictive biomarker in kidney cancer.

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Acknowledgments

The study was supported by a grant (SAF2012-40206) from the Spanish Ministry of Economy and Innovation (to Dr. Sánchez-Carbayo). The authors would like to thank all the members of his laboratory at the Translational Oncology Lab, and those at the previous Tumor Markers Group at the Spanish National Cancer Center for their technical support and constructive suggestions in the preparation of this manuscript. Finally, we would like to acknowledge the members of our clinical collaborators at the different institutions involved in this study, for their support in facilitating the tumor specimens as well as the clinical follow-up of the bladder cancer cases analyzed in this study.

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Authors and Affiliations

  1. Translational Oncology Laboratory, Ikerbasque Research Program, Medicine Department, University of the Basque Country, Vitoria-Gasteiz, Spain

    N. Pompas-Veganzones, V. Sandonis & Marta Sanchez-Carbayo

  2. Urology Department, Hospital Puerta Del Mar, Urology, Cadiz, Spain

    Alberto Perez-Lanzac & J. L. Alvarez-Ossorio

  3. Pathology Department, Hospital Puerta Del Mar, Cadiz, Spain

    M. Beltran

  4. Urology Department, Hospital De Jerez, Jerez, Spain

    P. Beardo & A. Juárez

  5. Urology Department, Hospital Virgen De Las Nieves, Granada, Spain

    F. Vazquez & J. M. Cozar

Authors
  1. N. Pompas-Veganzones
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  2. V. Sandonis
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  3. Alberto Perez-Lanzac
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  4. M. Beltran
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  5. P. Beardo
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  8. J. M. Cozar
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  9. J. L. Alvarez-Ossorio
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  10. Marta Sanchez-Carbayo
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Correspondence to Marta Sanchez-Carbayo.

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Pompas-Veganzones, N., Sandonis, V., Perez-Lanzac, A. et al. Myopodin methylation is a prognostic biomarker and predicts antiangiogenic response in advanced kidney cancer. Tumor Biol. 37, 14301–14310 (2016). https://doi.org/10.1007/s13277-016-5267-8

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  • DOI: https://doi.org/10.1007/s13277-016-5267-8

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