Identification of new biomarkers for sarcopenia and characterization of cathepsin D biomarker

Corine L'hôte, Benoît Cordier, Alain Labasse, Christelle Boileau, Bérénice Costes, Yves Henrotin
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引用次数: 8

Abstract

Background

Sarcopenia is the progressive generalized loss of skeletal muscle mass, strength, and function that occurs with aging. This study was undertaken to identify new biomarkers of sarcopenia by proteomics analysis of female sera.

Methods

A case–control study was set up, for which 19 sarcopenic subjects and 20 control subjects, according to the European Working Group on Sarcopenia Older People criteria published in 2010 (EWGSOP1), were enrolled. All the subjects were at least 65 years old and in majority female. Biomarker screening was performed by a comparative mass spectrometry analysis. Protein expression levels between the two groups were compared. One of the identified biomarkers, cathepsin D, was measured by immunoassay on the serum of the full sample set (n = 39). Its diagnostic performance was evaluated with a receiver operating characteristic curve (ROC curve).

Results

Two biomarkers were identified: fructose-biphosphate aldolase A (P ≤ 0.05) and cathepsin D (P ≤ 0.05). The levels of all of them were higher in sarcopenic patients. It was confirmed by immunoassay that cathepsin D levels in serum were significantly higher in the sarcopenic group of patients (P = 0.038). An inverse correlation (−0.385) was observed between cathepsin D levels in serum and gait speed. The area under the ROC curve measurement (AUC = 0.696) demonstrated that cathepsin D levels could discriminate between sarcopenic and non-sarcopenic subjects. A predictive model including cathepsin D, age, and body mass index was established to improve the diagnostic performance (AUC = 0.908).

Conclusions

Cathepsin D has been identified as a diagnostic biomarker of sarcopenia.

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肌少症新标志物的鉴定及组织蛋白酶D生物标志物的鉴定
骨骼肌减少症是随着年龄增长而发生的骨骼肌质量、力量和功能的进行性全身性丧失。本研究旨在通过对女性血清的蛋白质组学分析,寻找新的肌肉减少症的生物标志物。方法采用病例对照研究,根据欧洲老年人肌少症工作组2010年发布的标准(EWGSOP1),选取19名肌少症患者和20名对照患者。所有受试者年龄均在65岁以上,以女性居多。通过比较质谱分析进行生物标志物筛选。比较两组间蛋白表达水平。鉴定的生物标志物之一,组织蛋白酶D,通过免疫分析法在全样本组(n = 39)的血清中进行测定。采用受试者工作特征曲线(ROC曲线)评价其诊断效果。结果鉴定出两个生物标志物:果糖-二磷酸醛缩酶A (P≤0.05)和组织蛋白酶D (P≤0.05)。在肌肉减少症患者中,这些物质的含量都较高。免疫分析证实,肌减少组患者血清组织蛋白酶D水平明显升高(P = 0.038)。血清组织蛋白酶D水平与步态速度呈负相关(- 0.385)。ROC曲线下面积测量(AUC = 0.696)表明,组织蛋白酶D水平可以区分肌肉减少症和非肌肉减少症受试者。建立包括组织蛋白酶D、年龄和体重指数在内的预测模型以提高诊断效能(AUC = 0.908)。结论:组织蛋白酶D已被确定为肌少症的诊断性生物标志物。
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