Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis

Background Increasing studies have uncovered aberrant expression of homeobox (HOX) proteins in gastric cancer (GC), which is critically associated with prognosis and clinicopathological characteristics of GC. This study was conducted to investigate the clinical value and potential acting mechanisms of HOX proteins in GC. Methods A comprehensive search on PubMed, Embase, Web of Science and Cochrane Library was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) and the pooled odds ratio (OR) with its 95% CI were used to assess the effect of HOX proteins expression on the prognosis and clinicopathological features of GC, respectively. Results A total of 19 studies involving 3775 patients were selected for this study. Heterogeneity among HRs of overall survival (OS) was markedly high (I 2 = 90.5%, p = 0.000). The subgroup analysis showed that elevated expression of HOX proteins in the down-regulated subgroup was associated with a good prognosis in GC. (pooled HR: 0.46, 95% CI: 0.36–0.59, I 2 = 3.1%, p = 0.377), while over-expressed HOX proteins in the up-regulated subgroup were related to poor OS. (pooled HR: 2.59, 95% CI: 1.79–3.74, I 2 = 73.5%, p = 0.000). The aberrant expression of HOX proteins was crucially related to the TNM stage, depth of tumor invasion, tumor size, lymph node metastasis, distant metastasis, vascular invasion, histological differentiation and Lauren classification in GC. In addition, the molecular mechanisms how HOX proteins regulate tumorigenesis and development of GC were also explored. Conclusions HOX proteins play vital roles in GC progression and might serve as prognostic markers for GC. Novel therapeutic strategies targeting HOX proteins might be promising for GC prevention and therapy.