Head and Neck Cancer Clinical Trial
Official title:
Role of Myostatin, Activin A and Follistatin Cachexia of ENT Cancers
The main objective of our study was to determine the modifications of blood myostatin and activin A concentrations associated with head and neck cancers. Secondary objectives consisted in studying their influence on the occurrence of cachexia, bringing the proof of a tumoral secretion of these factors, and then determining the effect of tumor removal.
Myostatin and activin A, two members of the superfamily TGF-β, have been shown to play a
role on skeletal muscle mass regulation. In Humans, high plasma concentrations of activin A
were observed in cancer patients, especially in cachectic subpopulations, suggesting their
involvement in the development of cachexia.
55 patients were included in the study : 32 in the cancer group (only squamous cell
carcinoma) and 23 in the control group. The patients underwent a complete nutritional
assessment and multiple samples : blood before and 7 days after surgery, skeletal muscle
biopsies, tumor biopsies. Plasma concentrations of myostatin, activin and follistatin were
measured before and after tumor removal surgery. Concentrations of myostatin, activin and
follistatin were also measured in an incubation medium of a tumor biopsy. Activin A and
follistatin plasma concentrations were significantly increased in the cancer group (320 vs.
203 pg/ml ; p <0.001) (3593 vs 2148 pg/ml ; p <0.001), while myostatin plasma concentration
was significantly decreased in this group (1542 vs. 2100 pg/ml ; p = 0.010). Surprisingly,
data of the 7th postoperative day showed an increase in plasma activin A concentration (379
vs 320 pg /ml ; p <0.001) while concentrations of myostatin and follistatin were not
modified. A high postoperative systemic inflammation is one hypothesis to explain these
later results. Myostatin, activin A and follistatin proteins were systematically detected in
the medium of tumor a 48 hour-incubation period, providing a strong proof of the tumor
production of these factors by squamous cell carcinoma. The activin A/myostatin/follistatin
is modified in the context of head and neck cancer. Activin A particularly seems to play a
role in the occurrence of cachexia while follistatin could have a protective role for
skeletal muscle mass. This system could aimed in therapeutic ways to reduce cachexia in a
context of cancer in order to improve the quality of life and survival of patients.
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