Abstract and Introduction
Abstract
Aims To investigate clinicopathological significance and prognostic implications of EphA3, CD133 and Ki-67 expression in colorectal cancer.
Methods EphA3, CD133 and Ki-67 expression was assessed in 201 cases of paraffin-embedded colorectal carcinoma and 60 cases of distal normal mucosal tissue by immunohistochemistry. Medical records were reviewed and clinicopathological analysis was performed. The differential expression of EphA3 and CD133 protein was detected in 20 cases of fresh resected colorectal carcinoma and 20 cases of matched normal mucosal tissue adjacent to the carcinoma by western blot.
Results The expression of EphA3 and CD133 in carcinoma was significantly higher than that in normal mucosal tissue (p=0.008; p=0.004). EphA3 and CD133 were positively correlated with tumour size (p=0.029; p=0.017), histological grade (all p=0.001), infiltrative depth (all p=0.00), lymph node metastasis (all p=0.00), distant metastasis (p=0.017; p=0.030) and TNM stage (all p=0.001). Patients with high expression of EphA3 and CD133 had the lowest survival (all p=0.001) (median survival time of EphA3 positive and negative cases: 34.0 and 72.0 months; median survival time of CD133 positive and negative cases: 34.0 and 77.0 months). Multivariate survival analysis showed that EphA3 and CD133 expression was correlated significantly with shortened survival in patients with colorectal cancer (Cox regression: p=0.001, HR=4.722, 95% CI 2.667 to 8.361; p=0.001, HR=5.224, 95% CI 2.622 to 10.405). EphA3, CD133 and Ki-67 expression in colorectal cancer had positive correlations with each other (all p=0.001).
Conclusions EphA3 and CD133 may play an important role in the development and progression of tumours, and thus become useful indicators for clinical assessment of tumour biological behaviour and prognosis in patients with colorectal carcinoma.
Introduction
Eph receptors (Ephs) are the largest family of receptor tyrosine kinases (RTK). They are divided into two groups, EphAs and EphBs. Ephs plays an important role in the development of nervous and vascular systems, and may be involved in carcinogenesis, and progression and prognosis of certain cancers. EphA3 is a member of the Eph family of receptors. Some studies have shown that the expression of EphA3 is associated with B and T cell malignant neoplasms. Some recent studies have indicated that EphA3 is overexpressed in renal carcinoma, hepatic carcinoma, melanoma and sarcoma. However, the expression or function of EphA3 in solid tumours has not been widely studied.
CD133 (also called prominin-1) is a transmembrane glycoprotein, with a molecular weight of 120 kDa. It was initially considered to be a marker of haematopoietic stem cells. Resent research suggests that CD133 is one of the most important cancer stem cell markers. It is overexpressed in various solid tumours, including retinoblastoma, teratocarcinoma, leukaemia, glioblastoma, colorectal carcinoma and gastric carcinoma. CD133 expression has been found in colorectal cancer as an independent prognostic marker for overall survival. Ki-67 is a well recognised nuclear antigen-specific marker of cellular proliferation and is mainly used to evaluate the activity of proliferation. The relationship between EphA3, CD133 and Ki-67 in colorectal cancer has not yet been investigated.
Colorectal cancer is a major cause of cancer-related morbidity and mortality. In the western world it is the second leading cause of death from cancer. The incidence of colorectal cancer has recently increased in China. Therefore, it is important assess its prognosis according to the expression of some new molecular markers. In this study, we analysed the association of EphA3, CD133 and Ki-67 expression in colorectal cancer with clinicopathological features. Their inter-relationships were also evaluated. It is hoped that this study will provide further understanding of the pathogenesis of this disease.