Document Type : Systematic Review and Meta-analysis
Authors
1
Department of Medical Biochemistry, Faculty of Medicine, Recep Tayyip Erdoğan University, Rize, Türkiye.
2
Al Mutma’innah Maa O Shishu Hospital, Rajarbag Shareef, Dhaka, Bangladesh.
3
Department of Biostatistics, Faculty of Medicine, Cukurova University, Adana, Türkiye.
4
Department of Translational Medicine, Faculty of Medicine, Cukurova University, Adana, Türkiye.
5
Department of Pulmonary, Faculty of Medicine, Cukurova University, Adana, Türkiye.
6
Division of Biochemistry, Department of Basic Medical Sciences, Faculty of Medicine, Recep Tayyip Erdoğan University, Rize, Türkiye.
Abstract
Background: Cystatin C (CysC) exhibits both tumor-promoting and tumor-suppressing effects. Although elevated circulating CysC levels have been reported in multiple cancer types, studies assessing its prognostic value have produced conflicting results. This study aims to resolve these discrepancies and clarify the role of CysC as a prognostic marker.Methods: A literature search was conducted in multiple databases. The pooled Hazard Ratio (HR) with a 95% confidence interval (CI) was calculated to assess the prognostic significance of CysC, while the Odds Ratio (OR) with a 95% CI was used to evaluate its clinicopathological associations in various cancers. Sources of heterogeneity were identified by performing subgroup and meta-regression analyses. The study was registered in PROSPERO. Results: Twelve studies comprising 7678 patients were included in the analysis. The study found that elevated CysC levels were associated with worse overall survival (OS); pooled HR = 1.60, 95% CI = 1.22–2.10; p = 0.0006, I² = 84%. Subgroup analyses indicated that renal cancer, follow-up time >2.5 years, and study location (China) were linked to worse survival, and all subgroups contributed to significant heterogeneity. Sensitivity analysis confirmed the robustness of the pooled results. Additionally, CysC levels correlated with T stage, N stage, TNM stage, and sex, but not with smoking. Conclusion: Elevated CysC is associated with worse overall survival, but significant heterogeneity warrants cautious interpretation.
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