Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC). However, the median overall survival (OS) benefit is only ~3 months, and sufficient biomarkers predicting treatment response are not available. The aim of the present study was to evaluate miRNA expression patterns from HCC tissue biopsies as potential biomarkers in patients under sorafenib treatment. Nineteen patients with advanced HCC treated with sorafenib were included. RNA was extracted from formalin-fixed paraffin-embedded (FFPE) liver biopsies. miRNA expression profiling of 818 mature miRNAs was performed using GeneChip® miRNA Array 2.0 (Affymetrix). Global miRNA patterns were assessed using unsupervised hierarchical clustering analysis (UCA), and specific miRNAs with correlation with disease control rate (DCR) or good OS were evaluated by pairwise supervised analyses. UCA divided the patients into three distinct groups by their miRNA expression patterns. However, DCR or OS did not correlate with these sub-groups. We have identified several miRNAs that correlated with either DCR or OS (P<0.05). However, with correction for multiple testing, these results did not reach statistical significance in this small cohort. Global miRNA analysis from very low input RNA deriving from liver biopsies showed distinctive clustering of molecular sub-groups in patients with intermediate and advanced HCC. Clinical response including OS under sorafenib did not correlate with global miRNA expression patterns, but we have identified candidate miRNAs for the prediction of DCR and OS to be evaluated in prospective studies and larger patient cohorts.
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Research Article|
August 27 2014
Feasibility of global miRNA analysis from fine-needle biopsy FFPE material in patients with hepatocellular carcinoma treated with sorafenib
Jan Peveling-Oberhag;
*Medizinische Klinik 1, Universitätsklinikum Frankfurt, Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
Correspondence: Dr Jan Peveling-Oberhag (email [email protected]).
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Claudia Döring;
Claudia Döring
†Senckenbergisches Institut für Pathologie, Universitätsklinikum Frankfurt, Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
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Sylvia Hartmann;
Sylvia Hartmann
†Senckenbergisches Institut für Pathologie, Universitätsklinikum Frankfurt, Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
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Natalie Filmann;
Natalie Filmann
‡Institut für Biostatistik und Mathematische Modellierung, Fachbereich Medizin, Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
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Angelika Mertens;
Angelika Mertens
*Medizinische Klinik 1, Universitätsklinikum Frankfurt, Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
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Albrecht Piiper;
Albrecht Piiper
*Medizinische Klinik 1, Universitätsklinikum Frankfurt, Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
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Eva Herrmann;
Eva Herrmann
‡Institut für Biostatistik und Mathematische Modellierung, Fachbereich Medizin, Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
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Martin-Leo Hansmann;
Martin-Leo Hansmann
†Senckenbergisches Institut für Pathologie, Universitätsklinikum Frankfurt, Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
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Stefan Zeuzem;
Stefan Zeuzem
*Medizinische Klinik 1, Universitätsklinikum Frankfurt, Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
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Jörg Trojan;
Jörg Trojan
1
*Medizinische Klinik 1, Universitätsklinikum Frankfurt, Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
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Martin-Walter Welker
Martin-Walter Welker
1
*Medizinische Klinik 1, Universitätsklinikum Frankfurt, Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
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Publisher: Portland Press Ltd
Received:
January 02 2014
Revision Received:
May 22 2014
Accepted:
June 24 2014
Accepted Manuscript online:
June 24 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2015 Biochemical Society
2015
Clin Sci (Lond) (2015) 128 (1): 29–37.
Article history
Received:
January 02 2014
Revision Received:
May 22 2014
Accepted:
June 24 2014
Accepted Manuscript online:
June 24 2014
Citation
Jan Peveling-Oberhag, Claudia Döring, Sylvia Hartmann, Natalie Filmann, Angelika Mertens, Albrecht Piiper, Eva Herrmann, Martin-Leo Hansmann, Stefan Zeuzem, Jörg Trojan, Martin-Walter Welker; Feasibility of global miRNA analysis from fine-needle biopsy FFPE material in patients with hepatocellular carcinoma treated with sorafenib. Clin Sci (Lond) 1 January 2015; 128 (1): 29–37. doi: https://doi.org/10.1042/CS20140007
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