Biomarkers and mechanisms associated with cancer‐induced cardiac cachexia: A systematic review

Introduction Cancer cachexia is a severe multifactorial syndrome 1 that affects up to 80% of patients with advanced cancer, causing death in 20–80% with no effective treatments. 2,3 It causes multi-organ alteration and loss of skeletal and cardiac (myocardium) muscle mass. 4,5 Cardiac muscle wasting may result from cardiac protein loss associated with increased oxygen consumption and energy expenditure, resulting in cardiac insufficiency. 5 It is hypothesized that significant tissue inflammation and oxidative stress during cancer progression cause cardiac wasting-associated cardiomyopathy, such as a thinned ventricular wall, local tissue hypoxia and arrhythmias. 6 This review provided available evidence of cancer-induced cardiac cachexia in human and non-human models by examining biomarkers and the contributing factors to the development and progression of cardiac cachexia. Peroxisome proliferator-activated receptor alpha (PPARα), collapse section carnitine (CPTIβ) mRNA, myosin heavy chain (MHC) and troponin gene expressions were downregulated. 10 Mammalian hearts rely on lipid oxidation for energy. Greater cardiac muscle loss was observed in male adenocarcinoma-bearing mice, indicating that estrogen may have a protective cardiac effect in females. 13 There was reduced gene expression of MAFbx and protein expression of MuRF1 in the myocardium compared with skeletal muscle. 7 MuRF1 protein (4.3-fold) and Atrogin (same as MAFbx gene) (3.8 fold) expressions were significantly higher in the hearts of mice with cancer cachexia than controls, indicating upregulation of the ubiquitin proteosome system (UPS). 12 The increased oxidative stress is linked to higher expression of xanthine oxidase and NADPH oxidase, releasing reactive oxygen species (ROS), leading to loss of functioning myocardium.