Unknown,Transcriptomics,Genomics,Proteomics

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Feasibility of global microRNA analysis from fine-needle biopsy FFPE material in patients with hepatocellular carcinoma treated with sorafenib

ABSTRACT: Tumor cells were microdissected from FFPE sections of hepatocellular carcinoma (HCC) samples. micro RNA expression were correlated to clinical outcome and sorafenib-therapy. miRNA was labeled with the Affymetrix FlashTag Biotin HSR RNA Labeling Kit 20 microdissected hepatocellular carcinoma samples with detailed clinical data

ORGANISM(S): Homo sapiens

SUBMITTER: Claudia DÃ¶ring

PROVIDER: E-GEOD-56059 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Feasibility of global miRNA analysis from fine-needle biopsy FFPE material in patients with hepatocellular carcinoma treated with sorafenib.

Peveling-Oberhag Jan J Döring Claudia C Hartmann Sylvia S Filmann Natalie N Mertens Angelika A Piiper Albrecht A Herrmann Eva E Hansmann Martin-Leo ML Zeuzem Stefan S Trojan Jörg J Welker Martin-Walter MW

Clinical science (London, England : 1979) 20150101 1

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 forma ...[more]

PMID: 24959956

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Project description:Background and aims: Liver transplantation (LT) is the most radical treatment for hepatocellular carcinoma (HCC) with high rates of long-term survival, but tumor recurrence after LT is an unresolved problem. The aim of our study was to identify predictive markers for tumor recurrence after liver transplantation. Methods: In a retrospective single-center study, we included all patients with LT for HCC in our institution (01/2007-12/2012). Beside demographic data, we analyzed course, bridging therapies, Serum-AFP, time point of tumor recurrence, as well as the correlation of imaging and histopathology of our recipients. Additionally, we performed a microarray analysis to identify different miRNA profiles of patients with and without HCC recurrence after LT. Single assay stem-loop real-time PCR (Q-RT-PCR) was used for validation of the results. Results: During the study period, we performed 92 LT in patients with HCC (22 women, 70 men). Twenty-two (23.9%) patients developed a recurrent HCC after LT. Our subgroup with tumor recurrence after LT, presented with a mean disease-free survival of 10 months (3-55 months) and an overall survival of 25.5 months (4-77 months). Milan criteria, AFP levels and pathologic grading had an influence on the tumor recurrence. Performing miRNA analysis, we could identify significant upregulation of 8 miRNAs and downregulation of another 5 miRNAs in patients with tumor recurrence. Consecutively, array data were successfully validated using Q-RT-PCR. Multivariate Cox regression, ROC analysis and Kaplan-Meier showed that a score consisting of two miRNAs and Milan criteria are an independent predictor for tumor recurrence-free survival. Conclusions: Despite careful selection of patients, an early recurrence of HCC after LT cannot be avoided completely. Reliable prognostic markers related to tumor biology are still missing. Analysis and validation of specific miRNAs combined with radiological parameters might lead to a promising strategy for the prediction of tumor recurrence, but prospective studies have to follow. 8 macrodissected hepatocellular carcinoma (recurrent HCC) and 10 macrodissected hepatocellular carcinoma (non-recurrent HCC).

Project description:The liverM-bM-^@M-^Ys remarkable capacity to regenerate allows it to carry out vital life-supporting functions despite unrelenting pathogen and toxin-induced injury. Unchecked, this capability also leads to cirrhosis, a burgeoning global disease burden. Existing animal models only partially recapitulate human liver regeneration, which hitherto has not been systematically studied. We investigated human liver regeneration in a unique model of liver transplantation. Here we show coordinated changes in expression of microRNA (miRNA) during regeneration that drive proliferation, innate immunity and angiogenesis. Failed regeneration is associated with distinct miRNAs enforcing cell cycle inhibition and DNA methylation. The miRNA expression associated with successful or failed regeneration when recapitulated in vitro, triggered expression of cardinal regeneration-linked genes promoting cell cycle entry or inhibition, respectively. Furthermore, inhibition of three miRNAs whose downregulation is associated with successful regeneration, induced proliferation in vitro. Our data indicate that human liver regeneration is orchestrated by distinct miRNAs determining cell cycle fate. Their manipulation may obviate the need for transplantation by enforcing successful regeneration in the liver and other solid organs. We compared a group of seven patients with successful regeneration (RG) after auxiliary liver transplant (ALT) to four patients who also had ALT but failed to regenerate (NRG). Regeneration was quantified by volume expansion using radiographic imaging; functional recovery was assessed using nuclear isotope scanning and hepatocellular regeneration using histology. Based on histological assessment, three time points were selected for both groups (RG and NRG). Biopsies were taken at the time of transplant and at different intervals post-transplant. Since sample acquisition was driven by clinical necessity, widely discrepant time intervals existed between T=1, T=2 and T=3 for the patients. RNA was extracted from archived histology samples of the RG and NRG, and miRNA expression was analysed using the Affymetrix GeneChip miRNA 1.0 assays. This submission does not include NRG samples taken at time point 3.

Dataset Information

Feasibility of global microRNA analysis from fine-needle biopsy FFPE material in patients with hepatocellular carcinoma treated with sorafenib

Publications

Feasibility of global miRNA analysis from fine-needle biopsy FFPE material in patients with hepatocellular carcinoma treated with sorafenib.

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