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

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 ba...

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Main Authors: Radspieler, Melissa Marie (Author) , Schindeldecker, Mario (Author) , Stenzel, Philipp J. (Author) , Försch, Sebastian (Author) , Tagscherer, Katrin (Author) , Herpel, Esther (Author) , Hohenfellner, Markus (Author) , Hatiboglu, Gencay (Author) , Roth, Wilfried (Author) , Macher-Göppinger, Stephan (Author)
Format: Article (Journal)
Language:English
Published: July 9, 2019
In: Oncology letters
Year: 2019, Volume: 18, Issue: 3, Pages: 2654-2660
ISSN:1792-1082
DOI:10.3892/ol.2019.10593
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3892/ol.2019.10593
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Author Notes: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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Summary: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.
Item Description:Gesehen am 05.03.2020
Physical Description:Online Resource
ISSN:1792-1082
DOI:10.3892/ol.2019.10593

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