Background : An increasing number of studies have described the aberrant expression of homeobox (HOX) proteins in gastric cancer (GC), which is critically associated with the prognosis and clinicopathological characteristics of GC. This study was conducted to investigate the clinical value and potential mechanisms of HOX proteins in GC. Methods : A comprehensive search of PubMed, EMBASE, Web of Science and Cochrane Library was performed in accordance with the Preferred Reporting Items for

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... atic 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 effects of HOX protein expression on the prognosis and clinicopathological features of GC, respectively. Results : Nineteen 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). According to the subgroup analysis, increased expression of HOX proteins in the downregulated subgroup was associated with a good prognosis for patients with GC (pooled HR: 0.46, 95% CI: 0.36-0.59, I 2 =3.1%, p=0.377), while the overexpression of HOX proteins in the upregulated subgroup correlated with a reduced 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 tumour invasion, tumour size, lymph node metastasis, distant metastasis, vascular invasion, histological differentiation and Lauren classification in patients with GC . In addition , the molecular mechanisms by which HOX proteins regulate the 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 are promising for GC prevention and therapy.