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

• Verfasst von: Radspieler, Melissa Marie [VerfasserIn]
• Verfasst von: Schindeldecker, Mario [VerfasserIn]
• Verfasst von: Stenzel, Philipp J. [VerfasserIn]
• Verfasst von: Försch, Sebastian [VerfasserIn]
• Verfasst von: Tagscherer, Katrin [VerfasserIn]
• Verfasst von: Herpel, Esther [VerfasserIn]
• Verfasst von: Hohenfellner, Markus [VerfasserIn]
• Verfasst von: Hatiboglu, Gencay [VerfasserIn]
• Verfasst von: Roth, Wilfried [VerfasserIn]
• Verfasst von: Macher-Göppinger, Stephan [VerfasserIn]
• Titel: Lamin-B1 is a senescence-associated biomarker in clear-cell renal cell carcinoma
• Verf.angabe: Melissa Marie Radspieler, Mario Schindeldecker, Philipp Stenzel, Sebastian Försch, Katrin E. Tagscherer, Esther Herpel, Markus Hohenfellner, Gencay Hatiboglu, Wilfried Roth, Stephan Macher-Goeppinger
• E-Jahr: 2019
• Jahr: July 9, 2019
• Umfang: 7 S.
• Fussnoten: Gesehen am 05.03.2020
• Titel Quelle: Enthalten in: Oncology letters
• Ort Quelle: Athens : Spandidos Publ., 2010
• Jahr Quelle: 2019
• Band/Heft Quelle: 18(2019), 3, Seite 2654-2660
• ISSN Quelle: 1792-1082
• DOI: doi:10.3892/ol.2019.10593
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: biomarker
• Sach-SW: kidney
• Sach-SW: lamin-B1
• Sach-SW: renal cell carcinoma
• Sach-SW: senescence
• K10plus-PPN: 169176146X

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.