Association between klotho expression and malignancies risk and progression: A meta-analysis.

BACKGROUND: We assessed the association between tissue klotho protein expression and the risk and progression of malignancies.

METHODS: We searched the electronic databases for the studies regarding the relationship between tissue klotho protein expression and risk/progression of malignancies through January 2018. We calculated the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to evaluate the impact of tissue klotho protein expression on malignancies. A fixed-effect model, or in the presence of heterogeneity, random- effect model was applied to calculate the combined ORs.

RESULTS: Eighteen studies were recruited in our pooled-analysis. Overall malignancies including liver cancer, pancreatic ductal adenocarcinoma (PDAC), ovarian cancer, esophageal squamous cell carcinoma (ESCC), neuroendocrine cancer, oral cancer and bladder cancer demonstrated significantly lower ORs than those in controls (p < 0.05). Malignancies with tissue klotho protein expression showed a pooled hazard ratio (95% CI 0.784-2.479). Malignancies with tissue klotho protein expression showed a similar OR (95% CI 0.732-1.335) of male/total to cases without tissue klotho protein expression. Malignancies with tissue klotho protein expression showed a markedly lower OR (95% CI 0.454-0.941) of metastasis compared with those without tissue klotho protein expression. Malignancies with tissue klotho protein expression showed a markedly higher OR (95% CI 1.041-1.800) of stage I-II/III-IVcompared with those without tissue klotho protein expression. Malignancies with tissue klotho protein expression showed a similar OR (95% CI 0.948-3.407) of differentiation to cases without tissue klotho protein expression. Sensitivity analysis did not change the overall results significantly. No marked publication bias was noted.

CONCLUSIONS: Tissue klotho protein expression was associated with a lower risk and progression of malignancies. Klotho may be a protective factor against malignancies risk/progression.