Gallagher, I.J., Stephens, N.A., MacDonald, A.J., Skipworth, R.J.E., Husi, H., Greig, C.A., Ross, J.A., Timmons, J.A. and Fearon, K.C.H. (2012) Suppression of skeletal muscle turnover in cancer cachexia: evidence from the transcriptome in sequential human muscle biopsies. Clinical Cancer Research, 18(10), pp. 2817-27. (doi: 10.1158/1078-0432.CCR-11-2133)
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Abstract
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.<p></p> 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).<p></p> 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.<p></p> 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.<p></p>
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Fearon, Prof Kenneth and Husi, Dr Holger |
Authors: | Gallagher, I.J., Stephens, N.A., MacDonald, A.J., Skipworth, R.J.E., Husi, H., Greig, C.A., Ross, J.A., Timmons, J.A., and Fearon, K.C.H. |
Subjects: | Q Science > QH Natural history > QH301 Biology |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | Clinical Cancer Research |
Publisher: | American Association for Cancer Research |
ISSN: | 1078-0432 |
ISSN (Online): | 1557-3265 |
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