激活素A和肌肉生长抑制素在人类癌症恶病质中的作用。

Role of Activin A and myostatin in human cancer cachexia.

作者信息

Loumaye Audrey, de Barsy Marie, Nachit Maxime, Lause Pascale, Frateur Lena, van Maanen Aline, Trefois Pierre, Gruson Damien, Thissen Jean-Paul

机构信息

Endocrinology, Diabetology, and Nutrition Department (A.L., M.N., P.L., D.G., J-P.T.), Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, 1200 Brussels, Belgium; Endocrinology and Nutrition (A.L., M.d.B., J-P. T.), and Dietetic Departments (L.F.), King Albert II Cancer Institute (L.F., A.v.M.), Medical Imaging (P.T.), and Laboratory Medicine Departments (D.G.), Cliniques Universitaires St-Luc, 1200 Brussels, Belgium.

出版信息

J Clin Endocrinol Metab. 2015 May;100(5):2030-8. doi: 10.1210/jc.2014-4318. Epub 2015 Mar 9.

DOI:10.1210/jc.2014-4318

PMID:25751105

Abstract

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.

摘要

背景

恶病质是一种多因素综合征，其特征是骨骼肌质量减少且营养支持不能完全逆转。最近的动物观察表明，某些肿瘤产生激活素A（ActA）和肌肉生长抑制素（Mstn）可能与癌症恶病质有关。

目的

我们的目标是研究ActA和Mstn在人类癌症恶病质发展中的作用。

设计/地点：ACTICA研究是一项横断面研究，于2012年1月至2014年3月前瞻性地纳入了一家三级医疗中心的患者。受试者/观察指标：152例结直肠癌或肺癌患者进行了临床、营养和功能评估。通过CT扫描、人体测量和生物电阻抗测量身体成分。测定血浆中ActA、Mstn和卵泡抑素的浓度。

结果

恶病质与瘦体重和脂肪量减少（p < 0.01和p < 0.001）、身体功能下降、生活质量降低以及症状增加（QLQC30；p < 0.001）相关。恶病质患者（CC）的厌食症（SNAQ评分< 14）比非恶病质患者（CNC）更常见（p < 0.001）。CC患者的ActA浓度高于CNC患者（+40%；p < 0.001），且与体重减轻呈正相关（R = 0.323；p < 0.001），与SNAQ评分呈负相关（R = -0.225；p < 0.01）。相比之下，CC患者的Mstn浓度低于CNC患者（-35%；p < 0.001）。