The clinical significance of CCBE1 expression in human colorectal cancer

Abstract

Purpose: The identification and discovery of prognostic markers for colorectal cancer (CRC) are of great clinical significance. CCBE1 is expressed in various tumors and its expression correlates with lymphangiogenesis and angiogenesis. However, the association between CCBE1 expression and CRC outcome has not been reported. The aim of this study was to investigate clinical significance of CCBE1 expression in CRC. Patients and methods: CCBE1 expression was examined in 30 pairs of fresh CRC tissues and compared with adjacent normal (AN) tissues using quantitative real-time PCR (qRT-PCR), Western blotting and immunohistochemistry (IHC) staining. Tissue microarray immunohistochemical staining was used to study the CCBE1 expression characteristics of 204 CRC patient samples collected from January 2002 to December 2007, and the relationship of CCBE1 with clinicopathological features and prognosis of CRC was analyzed. Results: CCBE1 was highly expressed in CRC tissues compared with matched AN tissues ( P =0.001). Moreover, high expression of CCBE1 was significantly associated with tumor differentiation, lymph node metastasis, vascular invasion, liver metastasis and TNM stage in CRC patients ( P ≤0.01). Kaplan–Meier survival analysis revealed that high CCBE1 expression, poor tumor differentiation, lymph node metastasis and vascular invasion were significantly associated (all P <0.001) with poor prognosis for patients. Furthermore, univariate and multivariate Cox analysis revealed that high CCBE1 expression, poor tumor differentiation, lymph node metastasis and vascular invasion were independent risk factors for both overall survival (OS) and disease-free survival (DFS) of CRC patients (all P <0.05). OS and DFS of 267 CRC patients from The Cancer Genome Atlas (TCGA) database showed the same trend (log-rank P =6e-04, HR [high] =2.4; log-rank P =0.0081, HR [high] =1.9). Conclusion: High levels of CCBE1 contribute to the aggressiveness and poor prognosis of CRC. CCBE1 can serve as a novel potential biomarker to predict CRC patients’ prognosis. Keywords: CCBE1, prognosis, colorectal cancer, CRC, survival analysis, TCGA