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

Radspieler,Melissa   Marie; Schindeldecker,Mario; Stenzel,Philipp; Försch,Sebastian; Tagscherer,Katrin  E.; Herpel,Esther; Hohenfellner,Markus; Hatiboglu,Gencay; Roth,Wilfried; Macher‑Goeppinger,Stephan

doi:10.3892/ol.2019.10593

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
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Affiliations: Institute of Pathology, University Medical Center Mainz, D‑55131 Mainz, Germany, Institute of Pathology, University Hospital Heidelberg, D‑69120 Heidelberg, Germany, Department of Urology, University Hospital Heidelberg, D‑69120 Heidelberg, Germany
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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