Abstract
BackgroundAn 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 action mechanisms of HOX proteins in GC.MethodsA comprehensive search of 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 protein expression on the prognosis and clinicopathological features of GC, respectively.ResultsNineteen studies containing 3775 patients were selected for this study. Heterogeneity among HRs of overall survival (OS) was markedly high (I2 = 90.5%, p = 0.000). According to the subgroup analysis, increased expression of HOX protein in the downregulated subgroup was associated with a good prognosis for patients with GC (pooled HR: 0.46, 95% CI: 0.36–0.59, I2 = 3.1%, p = 0.377), while overexpression of HOX protein in the upregulated subgroup was correlated with a reduced OS (pooled HR: 2.59, 95% CI: 1.79–3.74, I2 = 73.5%, p = 0.000). The aberrant expression of HOX protein 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 tumorigenesis and development of GC were also explored.ConclusionsHOX proteins play vital roles in GC progression, which might serve as prognostic markers and therapeutic targets for GC.
Highlights
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
The following exclusion criteria were used: (1) overlapping or duplicate data; (2) reviews, letters, case reports, conference abstracts, retracted articles, editorials, and full texts not published in English; (3) studies of cancer cells or animal models, or irrelevant studies; and (4) studies without adequate information for calculating hazard ratio (HR) and 95% Confidence interval (CI)
Reviews, editorials, letters, conference abstracts, retracted articles, full texts not published in English, and studies of cancer cells or animal models were excluded
Summary
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. Because embryogenesis and tumorigenesis share similar characteristics such as growth and differentiation, the deregulation of HOX protein has been observed in abnormal development and malignancy [3]. An increasing number of HOX proteins have been investigated in various tumours, including acute myeloid leukaemia [5], breast cancer [6], lung cancer [7], and digestive tract neoplasms [8,9,10]. The implications of HOX proteins in tumorigenesis and development of GC have been reported in many studies. The roles of HOX proteins in GC remain controversial
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