Universität zu Köln

Wagner, Britta Janina, Plum, Patrick Sven, Apel, Katharina, Scherer, Marie, Buchner, Denise, Brinkmann, Sebastian ORCID: 0000-0002-2901-6204, Buettner, Reinhard, Stippel, Dirk, Quaas, Alexander and Drebber, Uta (2021). Protein-loss of SWI/SNF-complex core subunits influences prognosis dependent on histological subtypes of intra- and extrahepatic cholangiocarcinoma. Oncol. Lett., 21 (5). ATHENS: SPANDIDOS PUBL LTD. ISSN 1792-1082

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Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy with a 5-year-survival rate of <10%, mainly due to diagnosis in advanced stages and limited therapeutic options in case of progressive disease. Recently, evidence has indicated that alterations in the SWI/SNF-complex (SWI/SNF) may have an important role in the tumorigenesis of CCA. SWI/SNF-related chromatin remodeling has been reported to be crucial for differentiation and tumor suppression, and loss-of-function mutations of SWI/SNF are present in 20% of human malignancies; however, at present, little is known about its relevance in CCA. In the present study, a cohort of 52 patients with the diagnosis of primary CCA was retrospectively collected. All patients underwent surgery with curative intent. Tissue microarray analysis was performed on each tumor for immunohistochemical loss-of-protein analysis of the SWI/SNF core subunits ARID1A, INI-1, BRG1, PBRM-1 and BRM, corresponding to the following CCA subtypes: Extrahepatic CCA (ECCA), small duct or large duct intrahepatic CCA (ICCA). Kaplan-Meier analysis was used to determine survival distribution and survival differences were evaluated by log-rank test. In total, 14 of 52 patients (similar to 35%) exhibited protein-loss of any tested SWI/SNF core subunit. Notably, 17% of patients exhibited a loss of ARID1a; this was the protein loss with the highest frequency. Patients with small and large duct ICCA with protein-loss of any tested SWI/SNF subunit exhibited significantly worse survival compared with the wild-type cohort with proficient protein expression (P=0.013 and P=0.002), whereas no significant survival difference was detected for patients with ECCA. SWI/SNF and its core subunits may be considered promising predictive and therapeutic targets, and require further investigation in patients with CCA.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wagner, Britta Janina UNSPECIFIED UNSPECIFIED UNSPECIFIED Plum, Patrick Sven UNSPECIFIED UNSPECIFIED UNSPECIFIED Apel, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Scherer, Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED Buchner, Denise UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinkmann, Sebastian UNSPECIFIED orcid.org/0000-0002-2901-6204 UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Stippel, Dirk UNSPECIFIED UNSPECIFIED UNSPECIFIED Quaas, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Drebber, Uta UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-573015
DOI:	10.3892/ol.2021.12610
Journal or Publication Title:	Oncol. Lett.
Volume:	21
Number:	5
Date:	2021
Publisher:	SPANDIDOS PUBL LTD
Place of Publication:	ATHENS
ISSN:	1792-1082
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57301