Open Access

Lamin‑B1 is a senescence‑associated biomarker in clear‑cell renal cell carcinoma

  • Authors:
    • Melissa Marie Radspieler
    • Mario Schindeldecker
    • Philipp Stenzel
    • Sebastian Försch
    • Katrin E. Tagscherer
    • Esther Herpel
    • Markus Hohenfellner
    • Gencay Hatiboglu
    • Wilfried Roth
    • Stephan Macher‑Goeppinger
  • View Affiliations

  • Published online on: July 9, 2019     https://doi.org/10.3892/ol.2019.10593
  • Pages: 2654-2660
  • Copyright: © Radspieler et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Clear‑cell renal cell carcinoma (ccRCC) is a von‑Hippel‑Lindau gene (VHL) associated tumor disease. In addition to activating the hypoxia inducible factor (HIF) dependent oxygen‑sensing pathway, VHL loss also has an impact on a HIF‑independent senescence program which functions as a tumorigenesis barrier. Lamin‑B1 is a nuclear intermediate filament protein that exhibits effects on chromatin structure and gene expression and acts as a senescence effector. In the present study, the expression and prognostic relevance of Lamin‑B1 in a large cohort of ccRCC patients was examined and the report presents initial functional data on possible therapeutic implications. The expression of Lamin‑B1 was measured by immunohistochemistry using a tissue microarray containing tumor tissue samples from 763 ccRCC patients. Chi‑squared tests, Kaplan‑Meier curves and Cox regression models were used to investigate the possible association between Lamin‑B1 expression, clinical and pathological characteristics and patient survival. High Lamin‑B1 expression was associated with poor clinical outcomes and multivariate Cox regression analyses revealed that Lamin‑B1 was an independent prognostic factor for cancer‑specific survival. Furthermore in vitro data suggested that Lamin‑B1 acted as a functional downstream senescence effector in RCC cell lines. In conclusion, patients affected by ccRCC with high Lamin‑B1 expression exhibit poor prognosis. Lamin‑B1 may serve as a tissue‑based biomarker for new therapeutic agents targeting therapy‑induced senescence.
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September 2019
Volume 18 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Radspieler, M.M., Schindeldecker, M., Stenzel, P., Försch, S., Tagscherer, K.E., Herpel, E. ... Macher‑Goeppinger, S. (2019). Lamin‑B1 is a senescence‑associated biomarker in clear‑cell renal cell carcinoma. Oncology Letters, 18, 2654-2660. https://doi.org/10.3892/ol.2019.10593
MLA
Radspieler, M. M., Schindeldecker, M., Stenzel, P., Försch, S., Tagscherer, K. E., Herpel, E., Hohenfellner, M., Hatiboglu, G., Roth, W., Macher‑Goeppinger, S."Lamin‑B1 is a senescence‑associated biomarker in clear‑cell renal cell carcinoma". Oncology Letters 18.3 (2019): 2654-2660.
Chicago
Radspieler, M. M., Schindeldecker, M., Stenzel, P., Försch, S., Tagscherer, K. E., Herpel, E., Hohenfellner, M., Hatiboglu, G., Roth, W., Macher‑Goeppinger, S."Lamin‑B1 is a senescence‑associated biomarker in clear‑cell renal cell carcinoma". Oncology Letters 18, no. 3 (2019): 2654-2660. https://doi.org/10.3892/ol.2019.10593