Is Ep-CAM Expression a Diagnostic and Prognostic Biomarker for Colorectal Cancer? A Systematic Meta-Analysis

Abstract

Background: Cancer stem cell (CSC) epithelial cell adhesion molecule (Ep-CAM) is frequently expressed in colorectal cancer (CRC). However, the clinical significance of Ep-CAM expression in CRC is not clear. This study evaluated whether Ep-CAM provided valuable insight as a molecular biomarker for CRC diagnosis and prognosis and the potential of Ep-CAM as a novel therapeutic target in CRC.

Methods: Publications were selected online using electronic databases. The pooled odds ratios (ORs) or hazard ratios (HRs) with their 95% confidence intervals (95% CIs), and the combined sensitivity, specificity, and area under the curve (AUC) were calculated and summarized.

Results: Eleven eligible articles published in English involving 4561 cases were analyzed in this study. Ep-CAM expression was significantly higher in CRC compared with normal controls, and its overexpression was negatively linked to tumor differentiation, tumor stage, vascular invasion, depth of tumor invasion, lymph node metastasis, distant metastasis, and tumor budding in CRC patients. The loss of Ep-CAM expression positively correlated with these characteristics. Multivariate analysis of loss of Ep-CAM expression correlated with a poor prognosis in disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). The pooled sensitivity, specificity and AUC values of Ep-CAM expression in patients with CRC vs. normal controls were 0.93, 0.90, and 0.94, respectively.

Conclusions: The present findings suggest that Ep-CAM expression may be associated with CRC carcinogenesis, while the loss of Ep-CAM expression is correlated with the progression, metastasis, and poor prognosis of CRC. Ep-CAM expression may be a useful biomarker for the clinical diagnosis of CRC.

Keywords: Biomarker; CRC; Diagnosis; Ep-CAM; Expression; Prognosis.

Fig. 1

Flow chart of the selection procedure.

Fig. 2

Forest plot showing the relationship between Ep-CAM expression and CRC in cancer vs. controls, CRC vs. normal controls: OR = 96.70, 95% CI = 34.85–268.29, P < 0.001; and CRC vs. benign colonic lesions: OR = 17.07, 95% CI = 0.12–2511.93, P = 0.265.

Fig. 3

Forest plot showing the relationship of Ep-CAM overexpression with some clinicopathological features of CRC, including tumor differentiation: OR = 0.25, 95% CI = 0.11–0.55, P = 0.001; clinical stage: OR = 0.52, 95% CI = 0.28–0.96, P = 0.036; and vascular invasion: OR = 0.44, 95% CI = 0.21–0.93, P = 0.032.

Fig. 4

Forest plot showing the association of Ep-CAM overexpression with other clinicopathological features of CRC, including depth of tumor invasion: OR = 0.73, 95% CI = 0.51–1.04, P = 0.078; lymph node metastasis: OR = 0.55, 95% CI = 0.42–0.71, P < 0.001; distant metastasis: OR = 0.35, 95% CI = 0.23–0.55, P < 0.001; tumor budding: OR = 0.18, 95% CI = 0.06–0.50, P = 0.001; and tumor location: OR = 0.86, 95% CI = 0.56–1.31, P = 0.486.

Fig. 5

Forest plot indicating the correlation of loss of Ep-CAM expression with some clinicopathological features of CRC, including tumor differentiation: OR = 4.05, 95% CI = 1.80–9.10, P = 0.001; clinical stage: OR = 1.92, 95% CI = 1.04–3.54, P = 0.036; and vascular invasion: OR = 2.18, 95% CI = 1.11–4.27, P = 0.024.

Fig. 6

Forest plot indicating the correlation of loss of Ep-CAM expression with other clinicopathological features of CRC, including depth of tumor invasion: OR = 1.38, 95% CI = 0.96–1.97, P = 0.078; lymph node metastasis: OR = 1.82, 95% CI = 1.40–2.37, P < 0.001; distant metastasis: OR = 2.82, 95% CI = 1.81–4.39, P < 0.001; tumor budding: OR = OR = 4.33, 95% CI = 1.70–11.05, P = 0.001; and tumor location: OR = 1.16, 95% CI = 0.76–1.77, P = 0.486.

Fig. 7

Summary receiver operating characteristics (SROC) estimation of Ep-CAM expression in patients with CRC vs. normal controls, sensitivity = 0.93 (95% CI = 0.90–0.96), specificity = 0.90 (95% CI = 0.74–0.97), and AUC = 0.94 (95% CI = 0.92–0.96).