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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| Hauptverfasser: | , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
July 9, 2019
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| In: |
Oncology letters
Year: 2019, Jahrgang: 18, Heft: 3, Pages: 2654-2660 |
| ISSN: | 1792-1082 |
| DOI: | 10.3892/ol.2019.10593 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3892/ol.2019.10593
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| Verfasserangaben: | Melissa Marie Radspieler, Mario Schindeldecker, Philipp Stenzel, Sebastian Försch, Katrin E. Tagscherer, Esther Herpel, Markus Hohenfellner, Gencay Hatiboglu, Wilfried Roth, Stephan Macher-Goeppinger |
| Zusammenfassung: | 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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| Beschreibung: | Gesehen am 05.03.2020 |
| Beschreibung: | Online Resource |
| ISSN: | 1792-1082 |
| DOI: | 10.3892/ol.2019.10593 |