Abstract
BackgroundCancer cachexia is a progressive wasting syndrome and the most prevalent characteristic of cancer in patients with advanced pancreatic adenocarcinoma. We hypothesize that genes expressed in wasted skeletal muscle of pancreatic cancer patients may determine the initiation and severity of cachexia syndrome.Experimental designWe studied gene expression in skeletal muscle biopsies from pancreatic cancer patients with and without cachexia utilizing Real-Imaging cDNA-AFLP-based transcript profiling for genome-wide expression analysis.ResultsOur approach yielded 183 cachexia-associated genes. Ontology analysis revealed characteristic changes for a number of genes involved in muscle contraction, actin cytoskeleton rearrangement, protein degradation, tissue hypoxia, immediate early response and acute-phase response.ConclusionsWe demonstrate that Real-Imaging cDNA-AFLP analysis is a robust method for high-throughput gene expression studies of cancer cachexia syndrome in patients with pancreatic cancer. According to quantitative RT-PCR validation, the expression levels of genes encoding the acute-phase proteins α-antitrypsin and fibrinogen α and the immediate early response genes Egr-1 and IER-5 were significantly elevated in the skeletal muscle of wasted patients. By immunohistochemical and Western immunoblotting analysis it was shown, that Egr-1 expression is significantly increased in patients with cachexia and cancer. This provides new evidence that chronic activation of systemic inflammatory response might be a common and unifying factor of muscle cachexia.
Highlights
Cancer cachexia is a progressive wasting syndrome and the most prevalent characteristic of cancer in patients with advanced pancreatic adenocarcinoma
Patient characteristics We studied skeletal muscle biopsy samples of 23 patients diagnosed with histologically proven adenocarcinoma of the pancreas and treated at the Department of Surgery, University of Heidelberg, between November 2004 and April 2005
We carried out the transcriptome-wide characterization of skeletal muscle biopsies utilizing the Real-Imaging cDNA-AFLP approach to identify those genes that are commonly induced in the skeletal muscle of pancreatic cancer patients either with or without muscle cachexia
Summary
Cancer cachexia is a progressive wasting syndrome and the most prevalent characteristic of cancer in patients with advanced pancreatic adenocarcinoma. We hypothesize that genes expressed in wasted skeletal muscle of pancreatic cancer patients may determine the initiation and severity of cachexia syndrome. Experimental design: We studied gene expression in skeletal muscle biopsies from pancreatic cancer patients with and without cachexia utilizing Real-Imaging cDNA-AFLP-based transcript profiling for genome-wide expression analysis. Pancreatic cancer remains one of the most deadly tumor types, with the highest death-to-incidence ratio of all cancers. With a 5-year survival rate of less than 5% and a death-to-incidence ratio of 0.99, pancreatic ductal adenocarcinoma is currently one of the most aggressive gastrointestinal carcinomas [1]. The development of cachexia occurs in most patients with resectable and with unresectable pancreatic cancer, whose resting energy expenditure is generally increased. It has been demonstrated that a complex cascade of inflammatory responses may mediate alteration in metabolic processes, contributing to the development of cancer cachexia [5]
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