Skeletal muscle of gastric cancer patients expresses genes involved in muscle regeneration

Abstract

Abstract. Experimental studies have suggested that defective skeletal muscle regeneration could contribute to muscle wasting in cancer patients. However, data in humans are still lacking. In this study we aimed to assess the expression of the genes involved in muscle regeneration in gastric cancer patients. The RNA expression of the genes involved in muscle regeneration was assessed in the rectus abdominis muscle of patients with gastric cancer (n=30) and in age-matched control subjects (n=8). The Pax7 expression was significantly increased in the muscle of gastric cancer patients, either in the first stages of the disease or in stages IIIA and B. The increased expression was present both in stages IA and B and in stages II and III. The MyoD espression was also higher in the cancer patients than in the controls. However, the increased MyoD expression was present only in stages IA and B and not in the more advanced stages of the disease. The Myf5 expression, as well as that of the neonatal isoform of Myosin Heavy Chain (nMHC) did not differ significantly between the cancer patients and the controls. The necdin expression was negligible in healthy adult muscles and was significantly up-regulated in the muscle of gastric cancer patients. Its expression was highly increased in stages IA and B while it was similar to the control in stages II and III. The results of the present study show that in the skeletal muscle of gastric cancer patients, the expression of the genes involved in muscle regeneration is increased with respect to the controls. IntroductionCancer cachexia is a debilitating and life-threatening syndrome characterised by anorexia, body weight loss, loss of adipose tissue and skeletal muscle (1). Cachexia accounts for at least 20% of deaths in neoplastic patients. Cancer cachexia significantly impairs the quality of life as well as the response to anti-neoplastic therapies, thus increasing the morbidity and mortality of cancer patients. Muscle wasting is the most important phenotypic feature of cancer cachexia and the principal cause of function impairment, fatigue and respiratory complications, mainly related to the hyperactivation of muscle proteolytic pathways. The loss of muscle protein, defined as muscle catabolism, occurs due to an imbalance between the rates of muscle protein synthesis and breakdown (1). In recent years, numerous studies have contributed to our understanding of the mechanisms underlying the increase of skeletal muscle protein breakdown in cancer cachexia and to the clarification of the relative contribution of different proteolytic pathways (2,3). Four major proteolytic systems exist in the skeletal muscle: The endosome-lysosome system that relies on the activity of acidic proteases, the caspases, the calpains, and the ubiquitinproteasome system (2,3). The bulk of muscle proteins (50-70%) exists in the actomyosin complexes and myofibrils, and in different catabolic conditions, contractile proteins in these complexes are degraded by the ubiquitin-proteasome system (4). However, the...