Universität zu Köln

Ihle, Michaela Angelika, Merkelbach-Bruse, Sabine, Hartmann, Wolfgang ORCID: 0000-0002-7609-5021, Bauer, Sebastian ORCID: 0000-0001-5949-8120, Ratner, Nancy, Sonobe, Hiroshi, Nishio, Jun, Larsson, Olle, Aman, Pierre, Pedeutour, Florence, Taguchi, Takahiro, Wardelmann, Eva, Buettner, Reinhard and Schildhaus, Hans-Ulrich (2016). HR23b expression is a potential predictive biomarker for HDAC inhibitor treatment in mesenchymal tumours and is associated with response to vorinostat. J. Pathol. Clin. Res., 2 (2). S. 59 - 72. HOBOKEN: WILEY. ISSN 2056-4538

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Abstract

Histone deacetylases (HDAC) are key players in epigenetic regulation of gene expression and HDAC inhibitor (HDACi) treatment seems to be a promising anticancer therapy in many human tumours, including soft tissue sarcomas. HR23b has been shown to be a potential biomarker for sensitivity to HDACi therapy in cutaneous T-cell lymphoma and hepatocellular carcinoma. We aimed to evaluate HR23b as a candidate biomarker for HDACi response in sarcomas and gastrointestinal stromal tumours (GIST). Therefore, HR23b expression was analysed comprehensively by western blot in sarcoma and GIST cell lines covering all major clinically relevant subtypes. MTT assay and ApoTox-Glo (TM) Triplex assay were performed after treatment with vorinostat, belinostat, mocetino-stat and entinostat. HR23b protein expression was measured under HDACi treatment. Furthermore, HR23b expression levels were immunohistochemically determined in a large set of 523 clinical samples from sarcoma and GIST patients. Western blot analyses showed that sarcomas differ significantly in their expression of HR23b protein. All HDACi were able to regulate proliferation and apoptosis in vitro. Sensitivity to vorinostat correlated significantly with HR23b protein expression. Immunohistochemical prevalence screening in clinical samples of relevant adult-type tumours revealed that 12.5% of sarcomas (among them malignant peripheral nerve sheath tumours, pleomorphic liposarcomas, leiomyosarcomas, dedifferentiated liposarcomas, synovial sarcomas and angiosarcomas) and 23.2% of GIST show high HR23b expression. Therefore, HDACi have antiproliferative and proapoptotic effects in sarcomas depending on the expression level of HR23b. These findings suggest that HR23b represents a candidate biomarker for HDACi sensitivity in certain sarcoma types and in GIST.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ihle, Michaela Angelika UNSPECIFIED UNSPECIFIED UNSPECIFIED Merkelbach-Bruse, Sabine UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Wolfgang UNSPECIFIED orcid.org/0000-0002-7609-5021 UNSPECIFIED Bauer, Sebastian UNSPECIFIED orcid.org/0000-0001-5949-8120 UNSPECIFIED Ratner, Nancy UNSPECIFIED UNSPECIFIED UNSPECIFIED Sonobe, Hiroshi UNSPECIFIED UNSPECIFIED UNSPECIFIED Nishio, Jun UNSPECIFIED UNSPECIFIED UNSPECIFIED Larsson, Olle UNSPECIFIED UNSPECIFIED UNSPECIFIED Aman, Pierre UNSPECIFIED UNSPECIFIED UNSPECIFIED Pedeutour, Florence UNSPECIFIED UNSPECIFIED UNSPECIFIED Taguchi, Takahiro UNSPECIFIED UNSPECIFIED UNSPECIFIED Wardelmann, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED Buettner, Reinhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Schildhaus, Hans-Ulrich UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-280556
DOI:	10.1002/cjp2.35
Journal or Publication Title:	J. Pathol. Clin. Res.
Volume:	2
Number:	2
Page Range:	S. 59 - 72
Date:	2016
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	2056-4538
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HISTONE DEACETYLASE INHIBITOR; SUBEROYLANILIDE HYDROXAMIC ACID; PHASE-II TRIAL; GASTROINTESTINAL STROMAL TUMORS; T-CELL LYMPHOMA; KINASE INHIBITORS; CLINICAL-TRIAL; BELINOSTAT; CANCER; APOPTOSIS Multiple languages Pathology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28055