期刊
CLINICAL CANCER RESEARCH
卷 18, 期 10, 页码 2817-2827出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-11-2133
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资金
- Translational Medicine Research Collaboration-a consortium of the University of Aberdeen
- Translational Medicine Research Collaboration-a consortium of the University of Dundee
- Translational Medicine Research Collaboration-a consortium of the University of Edinburgh
- Translational Medicine Research Collaboration-a consortium of the University of Glasgow
- Grampian Health Board
- Tayside Health Board
- Lothian Health Board
- Greater Glasgow and Clyde Health Board
- Scottish Enterprise
- Wyeth Pharmaceuticals
- CRUK
- NCRI
- Aileen Lynn Bequest Fund
Purpose: The mechanisms underlying muscle wasting in patients with cancer remain poorly understood, and consequently there remains an unmet clinical need for new biomarkers and treatment strategies. Experimental Design: Microarrays were used to examine the transcriptome in single biopsies from healthy controls (n = 6) and in paired biopsies [pre-resection baseline (weight-loss 7%) and 8 month post-resection follow-up (disease-free/weight-stable for previous 2 months)] from quadriceps muscle of patients with upper gastrointestinal cancer (UGIC; n = 12). Results: Before surgery, 1,868 genes were regulated compared with follow-up (false discovery rate, 6%). Ontology analysis showed that regulated genes belonged to both anabolic and catabolic biologic processes with overwhelming downregulation in baseline samples. No literature-derived genes from preclinical cancer cachexia models showed higher expression in baseline muscle. Comparison with healthy control muscle (n = 6) revealed that despite differences in the transcriptome at baseline (941 genes regulated), the muscle of patients at follow-up was similar to control muscle (2 genes regulated). Physical activity (step count per day) did not differ between the baseline and follow-up periods (P = 0.9), indicating that gene expression differences reflected the removal of the cancer rather than altered physical activity levels. Comparative gene expression analysis using exercise training signatures supported this interpretation. Conclusions: Metabolic and protein turnover-related pathways are suppressed in weight-losing patients with UGIC whereas removal of the cancer appears to facilitate a return to a healthy state, independent of changes in the level of physical activity. Clin Cancer Res; 18(10); 2817-27. (C)2012 AACR.
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