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Meta-Analysis
. 2018 Jun 3;14(9):1041-1053.
doi: 10.7150/ijbs.25711. eCollection 2018.

Aberrant Levels of Cystatin C in Amyotrophic Lateral Sclerosis: a Systematic Review and Meta Analysis

Yu Zhu  1 , Mi Yang  1 , Fangjun Li  1 , Menghua Li  1 , Zhenzhen Xu  1 , Fang Yang  1 , Yue Liu  1 , Wenzhi Chen  1 , Yougen Zhang  1 , Renshi Xu  1
Affiliations
Meta-Analysis

Aberrant Levels of Cystatin C in Amyotrophic Lateral Sclerosis: a Systematic Review and Meta Analysis

Yu Zhu et al. Int J Biol Sci. .

Abstract

Evidences suggest that Cystatin C (Cys C) levels might be a biomarker in amyotrophic lateral sclerosis (ALS) diagnosis, but the conclusion is still in doubts. We conducted a systematic review and meta analysis of Cys C levels in cerebrospinal cord fluid (CSF) and peripheral blood of patients with ALS in order to further confirm whether or not Cys C levels is a biomarker in ALS diagnosis. The English relevant studies without year limitation were systematically searched in PubMed, EMBASE, Web of Science databases. The searched term contained "Amyotrophic Lateral Sclerosis" or "Motor Neuron Diseases" and "Cystatin C" and "Cerebrospinal fluid" or "CSF" or "Biomarker" or "Serum" or "Plasma" or "Blood". Observational studies reporting the associations between Cys C levels and ALS patients were selected to conduct a systematic review and meta analysis. Two reviewers performed the selection of this study independently. The Newcastle-Ottawa Scale assesses the quality and risk of bias of selected studies. Estimates were pooled using a random-effects model. The Cys C levels of CSF or peripheral blood in ALS patients compared with health controls (HCs) and several relevant neurodegenerative diseases (NDDs). Sixteen studies were included in our systematic review, 9 of them were selected to perform the meta analysis. Of these, eight studies measured Cys C levels in CSF and three studies measured it in blood. Cys C levels in CSF were significantly lower in ALS patients than in HCs (Hedge's g = -1.398, 95%CI: -2.43 to -0.36; p = 0.008), but there was no statistical difference between ALS patients and several relevant NDDs. No statistically significant difference in the Cys C levels of blood in the comparison between ALS and HCs. The correlation meta analysis presented no significant correlation between Cys C levels in CSF and age or disease duration respectively. Cys C levels significantly decrease in the CSF of ALS patients, but are not a specific biomarker for this disease. Cys C levels in CSF might be an auxiliary diagnostic biomarker of ALS.

Keywords: Amyotrophic lateral sclerosis; Biomarker; Blood; Cerebrospinal fluid; Cystatin C.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
PRISMA 2009 flow diagram.
Figure 2
Figure 2
Meta analysis of Cys C levels in CSF of ALS patients versus health controls.
Figure 3
Figure 3
Sensitive analysis of Cys C levels in CSF of ALS patients versus health controls.
Figure 4
Figure 4
Cys C levels in CSF ALS versus HCs: subgroup analysis based on assay type (enzyme-linked immunoassay [ELISA] and non-ELISA), age-matched study and geography.
Figure 5
Figure 5
Meta analysis of CSF Cys C levels in ALS patients versus several relevant NDDs.
Figure 6
Figure 6
Sensitive analysis of CSF Cys C levels in ALS patients versus several relevant NDDs.
Figure 7
Figure 7
CSF Cys C in ALS versus several relevant NDDs: Subgroup analysis based on assay type (enzyme-linked immunoassay [ELISA] and non-ELISA), age-matched study and geography.
Figure 8
Figure 8
Meta analysis of Cys C levels in CSF of ALS patients versus MSA/NDDs.
Figure 9
Figure 9
Meta analysis of Cys C levels in peripheral blood of ALS patients versus health controls.
Figure 10
Figure 10
Meta analysis of correlation coefficient between Cys C levels in CSF of ALS patients, age and duration time of disease.
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