Combination of circulating CXCR4 and Bmi-1 mRNA in plasma: A potential novel tumor marker for gastric cancer

Abstract

Abstract. cell-free nucleic acids in plasma have been reported to be a novel tumor marker. However, their exact significance in gastric cancer is unclear. in the present study, we focused on circulating CXCR4 and Bmi-1 mrna in plasma and evaluated their diagnostic values for patients with gastric cancer. CXCR4 and Bmi-1 mrna levels, as well as levels of cea and ca19-9 proteins, were determined in the plasma of 89 gastric cancer patients. The levels of these markers were significantly higher in cancer patients than in healthy subjects; however, there was a decrease in their expression after surgery. The sensitivity of detection for the combination of circulating CXCR4 and Bmi-1 mrna was higher than the sensitivities of detection for cea and ca19-9. in patients expressing both genes, CXCR4 and Bmi-1 mrna levels were strongly correlated. expression of the two circulating genes was also strongly correlated with the CEA level, and was significantly associated with the age of the patient, histological type, clinical stage, extent of cell differentiation and gastric cancer metastasis. our results indicate that the combined expression of circulating CXCR4 and Bmi-1 mrna represents a novel tumor marker, superior to traditional markers such as cea and ca19-9, for the diagnosis and monitoring of gastric cancer. IntroductionGastric cancer is one of the most lethal malignant tumors worldwide, with a 5-year survival rate of only 30-40% in patients with aggressive-phase disease. lymph node metastases are found in most patients with advanced gastric cancer. However, treatment of early-stage disease results in higher survival rates (1). Thus, the early detection of gastric cancer and prediction of the metastatic potential of the tumor are necessary to improve the survival rate.it has been reported that the chemokine cXc receptor 4 (cXcr4) and the cXcl12 ligand are involved in the metastasis of various types of cancer, including gastric carcinoma (2). The CXCR4 gene is located on the long arm of chromosome 2 and encodes 352 amino acids. The protein is a seven-transmembrane domain-containing G protein-coupled receptor, and is the unique high-affinity receptor for CXCL12 (3). It has been demonstrated that cancer cells express chemokine receptors, and that their corresponding ligands are frequently expressed at the site of tumor metastasis (4,5). Muller et al revealed that CXCR4 was highly expressed in human breast cancer cells and their distal metastases, while CXCL12 expression was increased at the common sites of breast cancer metastasis, such as the lymph nodes, lungs and liver (6). This indicates that CXCR4 is a potential tumor marker for predicting the locations and probability of tumor metastasis.The Bmi-1 gene is a member of the polycomb family that is located on the short arm of chromosome 10 and encodes a 326-amino acid protein. By deregulating two tumor suppressors, p16inK4a and p19arF (p14arF in humans), Bmi-1 can inhibit the apoptosis or senescence induced by p53 and prb (7,8). Furthermore, Bmi-1 plays a role in the act...

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