Role of Activin A and myostatin in human cancer cachexia.

CONTEXT: Cachexia is a multifactorial syndrome, characterized by the loss of skeletal muscle mass and not fully reversible by nutritional support. Recent animal observations suggest that production of Activin A (ActA) and Myostatin (Mstn) by some tumors might contribute to cancer cachexia.

OBJECTIVE

Our goal was to investigate the role of ActA and Mstn in the development of the human cancer cachexia.

DESIGN/

SETTING

The ACTICA study is a cross-sectional study, which prospectively enrolled patients from a tertiary-care center between January 2012 and March 2014. Subjects/Outcome Measures: One hundred fifty two patients with colorectal or lung cancer had clinical, nutritional and functional assessment. Body composition was measured by CT-scan, anthropometry, and bioimpedance. Plasma concentrations of ActA, Mstn, and Follistatin were determined.

RESULTS

Cachexia was associated with reduced lean and fat mass (p < .01 and p < .001), reduced physical function, lower quality of life, and increased symptoms (QLQC30; p < .001). Anorexia (SNAQ score < 14) was more common in cachectic patients (CC) than in noncachectic patients (CNC) (p < .001). ActA concentrations in CC patients were higher than in CNC patients (+40%; p < .001) and were correlated positively with weight loss (R = 0.323; p < .001) and negatively with the SNAQ score (R = -0.225; p < .01). In contrast, Mstn concentrations were decreased in CC patients compared to CNC patients (-35%; p < .001).

CONCLUSIONS

These results demonstrate an association between circulating concentrations of ActA and the presence of the anorexia/cachexia syndrome in cancer patients. Given the known muscle atrophic effects of ActA, our study suggests that increased circulating concentrations of ActA may contribute to the development of cachexia in cancer patients.