Downregulated E-cadherin expression indicates worse prognosis in Asian patients with colorectal cancer: evidence from meta-analysis.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Hematology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Xin
X
He
Zhigang
Z
Chen
Minyue
M
Jia
Xiaoying
X
Zhao
D044466:Asian People / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D011379:Prognosis; D016016:Proportional Hazards Models; D017594:Publication Bias
D015820:Cadherins