Downregulated E-Cadherin Expression Indicates Worse Prognosis in Asian Patients with Colorectal Cancer: Evidence from Meta-Analysis

• Published in: PloS one Vol. 8; no. 7; p. e70858
• Main Authors: He, Xin, Chen, Zhigang, Jia, Minyue, Zhao, Xiaoying
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.07.2013; Public Library of Science (PLoS)
• Subjects: Asian People - genetics; Biology; Cadherins - genetics; Cell adhesion & migration; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Down-Regulation; E-cadherin; Epithelial-Mesenchymal Transition; Gastroenterology; Gene Expression Regulation, Neoplastic; Genotype & phenotype; Hematology; Hospitals; Humans; Immunohistochemistry; Medical ethics; Medical prognosis; Medicine; Mesenchyme; Meta-analysis; Metastases; Metastasis; Neoplasm Grading; Neoplasm Staging; Odds Ratio; Patients; Prognosis; Proportional Hazards Models; Publication Bias; Quality; Studies; Tumors
• DOI: 10.1371/journal.pone.0070858
• ISSN: 1932-6203

Epithelial-mesenchymal transition (EMT) plays a crucial role in the progression and aggressiveness of colorectal carcinoma. E-cadherin is the best-characterized molecular marker of EMT, but its prognostic significance for patients with CRC remains inconclusive. Eligible studies were searched from the PubMed, Embase and Web of Science databases. Correlation between E-cadherin expression and clinicopathological features and prognosis was analyzed. Subgroup analysis was also performed according to study location, number of patients, quality score of studies and cut-off value. A total of 27 studies comprising 4244 cases met the inclusion criteria. Meta-analysis suggested that downregulated E-cadherin expression had an unfavorable impact on overall survival (OS) of CRC (n = 2730 in 14 studies; HR = 2.27, 95%CI: 1.63-3.17; Z = 4.83; P = 0.000). Subgroup analysis indicated that low E-cadherin expression was significantly associated with worse OS in Asian patients (n = 1054 in 9 studies; HR = 2.86, 95%CI: 2.13-3.7, Z = 7.11; P = 0.000) but not in European patients (n = 1552 in 4 studies; HR = 1.14, 95%CI: 0.95-1.35, Z = 1.39; P = 0.165). In addition, reduced E-cadherin expression indicated an unfavorable OS only when the cut off value of low E-cadherin expression was >50% (n = 512 in 4 studies; HR = 2.08, 95%CI 1.45-2.94, Z = 4.05; P = 0.000). Downregulated E-cadherin expression was greatly related with differentiation grade, Dukes' stages, lymphnode status and metastasis. The pooled OR was 0.36(95%CI: 0.19-0.7, Z = 3.03, P = 0.002), 0.34(95%CI: 0.21-0.55, Z = 6.61, P = 0.000), 0.49(95%CI: 0.32-0.74, Z = 3.02, P = 0.002) and 0.45(95%CI: 0.22-0.91, Z = 3.43, P = 0.001), respectively. This study showed that low or absent E-cadherin expression detected by immunohistochemistry served as a valuable prognostic factor of CRC. However, downregulated E-cadherin expression seemed to be associated with worse prognosis in Asian CRC patients but not in European CRC patients. Additionally, this meta-analysis suggested that the negative threshold of E-cadherin should be >50% when we detected its expression in the immunohistochemistry stain.