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Clinical classification of cancer cachexia: phenotypic correlates in human skeletal muscle

Johns, Neil and Hatakeyama, Shinji and Stephens, NA and Degen, Simone and Degen, Martin and Frieauff, W and Lambert, Christian and Greig, C and McDonald, CA and Ross, JA and Roubenoff, Ronenn and Glass, David and Jacobi, Carsten and Kenneth CH, Fearon (2014) Clinical classification of cancer cachexia: phenotypic correlates in human skeletal muscle. PLOS one.

Abstract

Aim – To relate muscle phenotype to a range of current diagnostic criteria for cancer cachexia

Methods – 41 patients with resectable upper gastrointestinal (GI) or pancreatic cancer underwent characterisation for cachexia based on weight-loss (WL) and / or low muscularity (LM). Four diagnostic criteria were used >5%WL, >10% WL, LM, and LM + >2%WL. Patients underwent biopsy of the rectus muscle. Analysis included immunohistochemistry for fibre size and type, protein and nucleic acid concentration, and Western blots for markers of autophagy, SMAD signalling, and inflammation.

Results – Compared with non-cachectic cancer patients, if patients were classified by LM or LM + >2%WL, mean muscle fibre diameter was significantly reduced (p = 0.02 and p = 0.001) repectively. No difference in fibre diameter was observed if patients were classified with WL alone. Regardless of classification, there was no difference in fibre number or proportion of fibre type across all myosin heavy chain isoforms. Mean muscle protein content was reduced and the ratio of RNA/DNA decreased if patients were classified by either >5% WL or LM + >2%WL. Compared with non-cachectic patients, when patients were classified according to >5% WL, SMAD3 protein levels were increased (p=0.022) and with >10% WL, beclin (p = 0.05) and ATG5 (p = 0.01) protein levels were also increased. There were no differences in pNFkB or pSTAT3 levels across any of the groups.

Conclusions – Whereas fibre type is not targeted selectively, muscle fibre size, biochemical composition and pathway phenotype can vary according to whether the criteria for cachexia include both a measure of low muscularity and weight loss.

Item Type: Article
Date Deposited: 26 Apr 2016 23:46
Last Modified: 26 Apr 2016 23:46
URI: https://oak.novartis.com/id/eprint/10704

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