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循环肌生成抑制素作为癌症或肥胖个体肌肉量和肌肉力量的生物标志物。

Circulating myostatin as a biomarker of muscle mass and strength in individuals with cancer or obesity.

机构信息

Research Laboratory of Endocrinology, Diabetes, and Nutrition, Institute of Experimental and Clinical Research, Université Catholique de Louvain, 55 Avenue Hippocrate, 1200 Brussels, Belgium; Department of Endocrinology and Nutrition, Cliniques Universitaires Saint-Luc, 10 Avenue Hippocrate, 1200 Brussels, Belgium.

Research Laboratory of Endocrinology, Diabetes, and Nutrition, Institute of Experimental and Clinical Research, Université Catholique de Louvain, 55 Avenue Hippocrate, 1200 Brussels, Belgium.

出版信息

Clin Nutr. 2024 Jul;43(7):1800-1808. doi: 10.1016/j.clnu.2024.05.046. Epub 2024 May 31.

Abstract

BACKGROUND & AIMS: Our study aims to determine whether myostatin (MSTN) is associated with muscle mass and strength in individuals with cancer or obesity, as well as with cancer cachexia (CC) or sarcopenic obesity (SO).

METHODS

The ACTICA study included individuals with CC (n = 70) or without CC (NC, n = 73). The MYDIASECRET study included individuals with obesity evaluated before (T0) and 3 months (T3) after bariatric surgery (n = 62). Body composition was assessed using bioelectrical impedance analysis (BIA). Skeletal muscle mass (SMM) and appendicular SMM (ASMM) were calculated from Janssen's and Sergi's equations, respectively, and expressed as indexes (SMMI and ASMMI). Handgrip strength (HGS) was assessed using a Jamar hand-held dynamometer. MSTN plasma levels were measured using ELISA. Spearman's coefficient was used to correlate MSTN with muscle mass and strength. Receiver operating characteristic (ROC) curve analysis was performed to identify an optimal MSTN cutoff level for the prediction of CC or SO.

RESULTS

In the ACTICA study, muscle mass and strength were lower in CC individuals than in NC individuals (SMMI: 8.0 kg/mvs 9.0 kg/m, p = 0.004; ASMMI: 6.2 kg/mvs 7.2 kg/m, p < 0.001; HGS: 28 kg vs 38 kg, p < 0.001). MSTN was also lower in CC individuals than in NC individuals (1434 pg/mL vs 2149 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN (SMMI: R = 0.500, p < 0.001; ASMMI: R = 0.479, p < 0.001; HGS: R = 0.495, p < 0.001). ROC curve analysis showed a MSTN cutoff level of 1548 pg/mL (AUC 0.684, sensitivity 57%, specificity 75%, p < 0.001) for the prediction of CC. In the MYDIASECRET study, muscle mass and strength were reduced at T3 (SMMI: -8%, p < 0.001; ASMMI: -12%, p < 0.001; HGS: -6%, p = 0.005). MSTN was also reduced at T3 (1773 pg/mL vs 2582 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN at T0 and T3 (SMMI-T0: R = 0.388, p = 0.002; SMMI-T3: R = 0.435, p < 0.001; HGS-T0: R = 0.337, p = 0.007; HGS-T3: R = 0.313, p = 0.013). ROC curve analysis showed a MSTN cutoff level of 4225 pg/mL (AUC 0.835, sensitivity 98%, specificity 100%, p = 0.014) for the prediction of SO at T3.

CONCLUSIONS

MSTN is positively correlated with muscle mass and strength in individuals with cancer or obesity, suggesting its potential use as a biomarker of muscle mass and strength. The ROC curve analysis suggests the potential use of MSTN as a screening tool for CC and SO.

摘要

背景与目的

本研究旨在确定肌肉生长抑制素(MSTN)是否与癌症或肥胖患者的肌肉量和肌肉力量有关,以及是否与癌症恶病质(CC)或肌少症性肥胖(SO)有关。

方法

ACTICA 研究纳入了 CC 患者(n=70)或无 CC 的非癌症患者(NC,n=73)。MYDIASECRET 研究纳入了接受减重手术前(T0)和术后 3 个月(T3)评估的肥胖患者(n=62)。使用生物电阻抗分析(BIA)评估身体成分。使用 Janssen 和 Sergi 方程分别计算骨骼肌质量(SMM)和四肢骨骼肌质量(ASMM),并表示为指数(SMMI 和 ASMMI)。使用 Jamar 手持测力计评估握力(HGS)。使用 ELISA 法测量 MSTN 血浆水平。使用 Spearman 系数将 MSTN 与肌肉量和力量相关联。进行受试者工作特征(ROC)曲线分析,以确定预测 CC 或 SO 的 MSTN 最佳截断值。

结果

在 ACTICA 研究中,CC 患者的肌肉量和力量均低于 NC 患者(SMMI:8.0 kg/m 比 9.0 kg/m,p=0.004;ASMMI:6.2 kg/m 比 7.2 kg/m,p<0.001;HGS:28 kg 比 38 kg,p<0.001)。CC 患者的 MSTN 水平也低于 NC 患者(1434 pg/mL 比 2149 pg/mL,p<0.001)。肌肉量和力量与 MSTN 呈正相关(SMMI:R=0.500,p<0.001;ASMMI:R=0.479,p<0.001;HGS:R=0.495,p<0.001)。ROC 曲线分析显示,MSTN 截断值为 1548 pg/mL(AUC 0.684,敏感性 57%,特异性 75%,p<0.001)可预测 CC。在 MYDIASECRET 研究中,T3 时肌肉量和力量均降低(SMMI:-8%,p<0.001;ASMMI:-12%,p<0.001;HGS:-6%,p=0.005)。MSTN 也在 T3 时降低(1773 pg/mL 比 2582 pg/mL,p<0.001)。T0 和 T3 时肌肉量和力量与 MSTN 呈正相关(SMMI-T0:R=0.388,p=0.002;SMMI-T3:R=0.435,p<0.001;HGS-T0:R=0.337,p=0.007;HGS-T3:R=0.313,p=0.013)。ROC 曲线分析显示,MSTN 截断值为 4225 pg/mL(AUC 0.835,敏感性 98%,特异性 100%,p=0.014)可预测 T3 时的 SO。

结论

MSTN 与癌症或肥胖患者的肌肉量和肌肉力量呈正相关,提示其可能作为肌肉量和肌肉力量的生物标志物。ROC 曲线分析提示 MSTN 可能作为 CC 和 SO 的筛查工具。

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