The prognostic value of E‐cadherin in gastric cancer: A meta‐analysis

Abstract

The prognostic impact of E-cadherin downregulation in gastric cancer has been assessed for years while the results are controversial and heterogeneous. We thus comprehensively reviewed the evidence for evaluation of E-cadherin expression in gastric cancer to determine this effect. We searched PubMed and Embase to identify eligible studies, and 26 studies comprising 4,383 gastric cancer patients were included to assess the association between E-cadherin immunohistochemical expression and overall survival (OS) and clinicopathological characteristics. Summary hazard ratios (HRs) or odds ratios (ORs) with 95% confidence interval (95% CI) were calculated to estimate the effect. We also performed meta-regression and subgroup analysis according to study location, publication year, number of patients, quality score of studies and cut-off value. Reduced E-cadherin expression was significantly correlated with poor OS of gastric cancer patients (HR 1.62, 95% CI 1.34-1.96). Subgroup analysis indicated that E-cadherin low-expression had an unfavorable impact on OS in Asian patients (HR 1.87, 95% CI 1.45-2.41). Moreover, downregulation of E-cadherin was significantly associated with TNM stage (OR 2.52, 95% CI 1.85-3.43), the depth of invasion (OR 2.01, 95% CI 1.39-2.90), lymph node metastasis (OR 2.39, 95% CI 1.68-3.40), distant metastasis (OR 2.23, 95% CI 1.21-4.11), grade of differentiation (OR 2.26, 95% CI 1.60-3.21), vascular invasion (OR 1.86, 95% CI 1.10-3.13) and histological type of gastric cancer (OR 4.22, 95% CI 2.96-6.02). This meta-analysis revealed that E-cadherin expression might be a predicative factor of poor prognosis for gastric cancer particularly in Asia.Despite the recent reduction in incidence, gastric cancer is still the second most frequent cause of cancer-related death worldwide, leading to 738,000 deaths worldwide in 2008. Much effort has been made for a long time to identify prognostic biomarkers in gastric cancer patients. Although genes associated with metastasis (e.g., MMP9), growth (e.g., EGF), apoptosis (e.g., p53) and angiogenesis (e.g., VEGF) have been investigated in recent studies, to identify an established marker possessing the predicative value for survival of gastric cancer patients remains a topic that needs to be explored.3-6 E-cadherin is the prototype of the cadherin family that links to catenins to form E-cadherin/catenin complex which is further linked to the actin cytoskeleton.7 Recent studies have shown that E-cadherin not only acts in infiltration and metastasis, but also has an important role of tumorsuppressor in numerous cancers comprising gastric cancer, providing the evidence that E-cadherin plays a vital role in the development and progression of gastric cancer and might be significantly associated with the prognosis of patients. 8,9 Low or absent E-cadherin expression, implicated in the pathogenesis of gastric cancer, was caused by several molecular mechanisms. Promoter hypermethylation is an import mechanism silencing tumor suppressors and has been found to be significa...

The prognostic role of Leucine-rich repeat-containing G-protein-coupled receptor 5 in gastric cancer: A systematic review with meta-analysis

“…To improve the clinical care of patients with gastric cancer, the identification of new, biologically relevant prognostic markers is necessary. Several molecular markers, such as matrix metalloproteinase 2 (MMP-2), E-cadherin, epidermal growth factor (EGF), p53 and vascular endothelial growth factor (VEGF), are associated with prognosis in patients with gastric cancer [4][5][6][7]. Within the category of biomarkers, Leucinerich repeat-containing G-protein-coupled receptor 5 (LGR5) expression has recently attracted significant attention.…”

Long Noncoding RNA HOTAIR as an Independent Prognostic Marker in Cancer: A Meta-Analysis

“…All eligible studies were scored as previously reported [12], [13]. The final scores are expressed as percentages, with a higher percentage denoting better methodological quality.…”

Comparative characteristics of the transcriptional activity of CDH1, CTNNB1 genes and the expression levels of E-cadherin, β-catenin proteins, coded by these genes, in intestinal-type gastric adenocarcinoma

“…B. Xing et al (2013) установили, что снижение уровня экспрессии Е-кадгерина ассоциировано со снижением общей выживаемости больных РЖ [19]. Кроме того, имеется связь между аберрантной экспрессией β-кате-нина в РЖ и степенью гистологической дифференци-ровки опухоли, наличием метастазов в лимфатических узах, а также отдалённых метастазов [5].…”