Role of TLR4 as a prognostic factor for survival in various cancers: a meta-analysis

Accumulating evidence showed that high expression of toll like receptor 4 (TLR4) was significantly associated with the outcome of patients with solid cancers. However, other studies failed to draw a similar conclusion. Thus, a systematic meta-analysis was performed to assess the prognostic value of TLR4 in solid tumors.

Data from 15 studies and 1294 patients were enrolled. Among the 15 studies, 14 studies demonstrated the association between overall survival(OS) and TLR4 expression, and 7 studies described the relationship between disease-free survival(DFS) and TLR4 expression. High expression of TLR4 was significantly associated with poor OS (pooled hazard ratio (HR) = 2.05; 95% confidence interval (CI) (1.49, 2,49), P < 0.001). The results of meta regression analysis indicated that the subgroups of ethnic (PD = 0.924), tumor type (PD = 0.669), HR obtained method (PD = 0.945), analysis type (PD = 0.898), and cut-off value(PD = 0.835) were not the resource of heterogeneity. Moreover, patients with elevated TLR4 had a significantly worse DFS (pooled HR = 1.79; 95% CI (1.11, 2.88), P < 0.05).

We searched PubMed, Embase and the Cochrane Library (last update by April 18, 2017) to identify literatures evaluating the value of TLR4 in cancer patients. Combined hazard ratios (HRs) for OS and DFS were assessed using fixed-effects models and random effects models respectively.

The meta-analysis suggests that elevated expression of TLR4 is associated with poor OS and shorter DFS of patients with solid tumors. The results indicate that TLR4, as a novel prognostic biomarker in solid tumors, could potentially help to improve treatment decision-making of solid tumors in clinical.