The prognostic and clinicopathologic characteristics of CD147 and esophagus cancer: A meta-analysis

Abstract

Objective: The prognostic significance of CD147 expression in esophageal cancer patients remains controversial. Using a meta-analysis, we investigated the prognostic and clinicopathologic characteristics of CD147 in esophageal cancer.

Methods: A comprehensive literature search of the PubMed (1966-2016), EMBASE (1980-2016), Cochrane Library (1996-2016), Web of Science (1945-2016), China National Knowledge Infrastructure (1982-2016), and Wanfang databases (1988-2016) was performed to identify studies of all esophageal cancer subtypes. Correlations between CD147 expression and survival outcomes and clinicopathological features were analyzed using meta-analysis methods.

Results: Seventeen studies were included. High CD147 expression reduced the 3-year survival rate (OR = 3.26, 95% CI = (1.53, 6.93), p = 0.02) and 5-year survival rate(OR = 4.35, 95% CI = (2.13, 8.90), p < 0.0001). High CD147 expression reduced overall survival in esophageal cancer (HR = 1.60, 95% CI = (1.19, 2.15), p = 0.02). Additionally, higher CD147 expression was detected in esophageal cancer tissues than noncancerous tissues (OR = 9.45, 95% CI = (5.39, 16.59), p < 0.00001), normal tissues (OR = 12.73, 95% CI = (3.49, 46.46), p = 0.0001), para-carcinoma tissues (OR = 12.80, 95% CI = (6.57, 24.92), p < 0.00001), and hyperplastic tissues (OR = 3.27, 95% CI = (1.47, 7.29), p = 0.004). CD147 expression was associated with TNM stage (OR = 3.66, 95% CI = (2.20, 6.09), p < 0.00001), tumor depth (OR = 7.97, 95% CI = (4.13, 15.38), p < 0.00001), and lymph node status (OR = 5.14, 95% CI = (2.03,13.01), p = 0.0005), but not with tumor differentiation, age, or sex.

Conclusion: Our meta-analysis suggests that CD147 is an efficient prognostic factor in esophageal cancer. High CD147 expression in patients with esophageal cancer was associated with worse survival outcomes and common clinicopathological indicators of poor prognosis.

Fig 1. Flowchart of selection of studies for inclusion in meta-analysis.

A total of 64 studies were identified, and 21 studies were excluded because of duplication. After reading the titles and abstracts, 20 studies were excluded. 23 possible full text studies were carefully reviewed (animal studies [n = 5]; review and meta-analysis [n = 2]; no control group [n = 2]). Finally, 17 trials were included for quantitative analysis.

Fig 2. Survival analysis forest plot.

The squares and horizontal lines correspond to the study- specific OR and 95%CI.The area of the squares reflects the study-specific weight (inverse of the variance). The diamonds represent the pooled OR and 95% CI. The solid vertical line is at the null value (OR = 1). A The relationship between CD147 expression and overall survival. CD147 expression was associated with overall survival (HR = 1.60, 95% CI = (1.19, 2.15), p = 0.02). B The relationship between CD147 expression and 3-year survival rate. CD147 expression was associated with 3-year survival rate (OR = 3.26, 95%CI = (1.53,6.93),p = 0.02). C The relationship between CD147 expression and 5-year survival rate.CD147 expression was associated with 5-year survival rate (OR = 4.35, 95%CI = (2.13, 8.90), p < 0.0001).

Fig 3. Forest plots of CD147 expression and different tissues.

The squares and horizontal lines correspond to the study-specific OR and 95% CI.The area of the squares reflects the study-specific weight (inverse of the variance). The diamonds represent the pooled OR and 95% CI. The solid vertical line is at the null value (OR = 1). A CD147 positive expression between cancer and noncancer tissues.Significant difference was found between cancer and noncancer tissues (OR = 9.45, 95%CI = (5.39, 16.59), p < 0.00001). B CD147 positive expression between cancer and normal tissues.Significant difference was found between cancer and normal tissues (OR = 12.73, 95%CI = (3.49, 46.46), p = 0.0001). C CD147positive expression between cancer and para-carcinoma tissues.Significant difference was found between cancer and para-carcinoma tissues (OR = 12.80, 95%CI = (6.57, 24.92), p < 0.00001). D CD147 positive expression between cancer and hyperplastic tissues.Significant difference was found between cancer and hyperplastic tissues (OR = 3.27, 95% CI = (1.47, 7.29), p = 0.004).

Fig 4. Forest plots of CD147 expression and the clinicopathological features of patients with esophagus cancer.

The squares and horizontal lines correspond to the study- specific OR and 95% CI.The area of the squares reflects the study-specific weight (inverse of the variance). The diamonds represent the pooled OR and 95% CI. The solid vertical line is at the null value (OR = 1). A The relationship between CD147 expression and TNM staging. CD147 expression was associated with TNM staging of esophagus cancer(OR = 3.66, 95%CI = (2.20, 6.09), p < 0.00001). B The relationship between CD147 expression and tumor depth. CD147 expression was associated with tumor depth (OR = 7.97, 95%CI = (4.13, 15.38), p < 0.00001). C The relationship between CD147 expression and status of lymph node.CD147 expression was associated with status of lymph node (OR = 5.14, 95%CI = (2.03, 13.01), p = 0.0005). D The relationship between CD147 expression and tumor differentiation.CD147 expression wasn’t associated with tumor differentiation (OR = 1.57, 95%CI = (0.79, 3.12), p = 0.19). E The relationship between CD147 expression and age.CD147 expression wasn’t associated with age (OR = 1.05, 95%CI = (0.72,1.53), p = 0.79). F The relationship between CD147 expression and sex.CD147 expression wasn’t associated with sex (OR = 0.70, 95%CI = (0.47, 1.04), p = 0.07).