Pretreatment elevated serum lactate dehydrogenase as a significant prognostic factor in malignant mesothelioma A meta-analysis

Background: Lactate dehydrogenase (LDH) as a hypoxia-regulator plays a vital role in alternative metabolic pathways of cancer cells. Numerous studies have assessed the prognostic value of elevated pretreatment LDH in malignant mesothelioma (MM). However, the results have been largely inconsistent. Hence, the aim of current study was to investigate the prognostic value of pretreatment LDH levels in patients with MM by performing a meta-analysis of relevant studies. Methods: A literature search for English language studies, which investigated the association of LDH levels with overall survival (OS) in malignant mesothelioma, was performed in the electronic databases, PubMed, Medline, Embase, and Web of Science. Pooled hazard ratios (HRs) and their 95% confidence intervals (95% CIs) were calculated. Heterogeneity was assessed using Cochran Q and I-2 statistics. Sensitivity analysis, meta-regression model, and subgroup analysis were performed to trace the source of heterogeneity, if applicable. Results: A total of 9 studies with a combined study population of 1977 patients came within the purview of this meta analysis. Pooled HR for OS in patients with high LDH level was 1.68 (95% CI=1.36-2.00). Significant heterogeneity was observed in the included studies (I-2=54.1%, P=0.026). Sensitivity analysis after sequential exclusion of 1 study at a time, and meta-regression with inclusion of 6 confounding factors failed to identify the source of heterogeneity. However, in the subgroup analysis, it was found that the publication of Nojiri et al was the origin of heterogeneity. When omitted the publication of Nojiri et al, the pooled HR of the rest 8 studies was 1.83 (95% CI=1.45-2.20, I-2=0.0%, P=0.723). Egger test and funnel plots excluded the possibility of publication bias affecting the results of the current meta-analysis. Conclusion: A negative association was observed between high LDH levels and poor overall survival in the current study. Our findings suggest that pretreatment LDH level could serve as a useful predictor of prognosis in patients with malignant mesothelioma.