Myostatin, activin-A and follistatin are produced by the tumor in head and neck cancer and likely contribute to sarcopenia: A case-control, cross-sectional exploratory study

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BACKGROUND AND AIMS: Myostatin (M), activin-A (A) and follistatin (F), three TGF-β superfamily members, play a role in cancer sarcopenia. The aim of our study was to assess the association of MAF in head and neck cancer (HNC) skeletal muscle loss. MATERIALS AND METHODS: This prospective study involved 55 patients, 32 with HNC and 23 controls. The patients underwent a full nutritional assessment just before surgery. Tumor, muscle and plasma were harvested at the time of surgery. Plasma was harvested a second time 7 days after the procedure. Tumor explants were cultured and MAF were measured in the incubation medium. RESULTS: A and F plasma levels were higher in cancer patients compared to control (320 vs. 203 pg/ml, p < 0.001, ES = 0.96 95 % CI [0.40; 1.52] and 3593 vs 2148 pg/ml, p < 0.001, ES = 1.10 95%CI [0.53; 1.66], respectively) and M plasma level lower (1542 vs. 2100 pg/ml, p = 0.01, ES = -0.70 95%CI [-1.24; -0.15]). M plasma level was correlated with the skeletal muscle index at the third lumbar vertebra (r = 0.44; p < 0.05) and negatively correlated with weight loss (r = -0.65; p < 0.05) and the C Reactive protein level (-0.44; p = 0.02). At the seventh postoperative day (D), A was increased (D7 vs D0) in the cancer group (379 vs 320 pg/ml; p < 0.001) while the concentrations of M and F were unchanged from the presurgical level. There was no difference between groups in the transcript levels of M and A in skeletal muscles. MAF were systematically detected in the tumor incubation medium with no correlation between tumor incubation medium level and plasma level at D0. CONCLUSION: The MAF secretory profile is modified in HNC. In particular, A seems to play a role in muscle loss while F protects against skeletal muscle mass loss.

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