Expression And Clinical Significance Of Bmi-1and Mel-18in Esophageal Squamous Cell Carcinoma

Esophageal cancer is the most common malignancy in the digest system. China is a high-incidence areas in the word. Among them, esophageal squamous cell carcinoma (ESCC) dominated, accounting for about90%.There are many traditional clinical diagnosis methods and histologic markers to detect this disease are commonly used today,but there are a variety of insufficients such as low specificity, poor sensitivity, operation trouble, traumatic check, et al. Diagnosis and treatment of ESCC at an early stage and reasonably judge therapeutic efficacy can conspicuously improve survival. So, there is an urgent need to seek a simple and effective way of diagnosis and prognostication for ESCC patients,and the research of cancer specific molecular markers has become a hot spot in recent years. Both Bmi-1and Mel-18belong to the Polycomb group, As an oncogene, Bmi-1plays an important role in cell proliferation and human oncogenesis. Overexpression of Bmi-1has been observed in a variety of human cancers,such as non-small cell lung cancer, gastric carcinoma, breast cancer, colorectal cancer,et al. Bmi-1has become a research focus in the tumor therapy field. The Mel-18gene product is structurally highly similar to Bmi-1protein,and there is a functional similarity too. One study has shown that Mel-18is overexpressed in Hodgkin’s Lymphoma,but more researches have shown that Mel-18plays a role as a suppressor gene in most tumors. There is low expression of Mel-18gene not only in hematological malignancies, but also in solid tumors, including breast and gastric carcinomas. Study of Bmi-1and Mel-18expression in esophageal cancer have reported fewer. We investigated the expression of Bmi-1and Mel-18in Esophageal Squamous cell Carcinoma cells strains and tissues to explore the expression and clinical significance of Bmi-1and Mel-18in Esophageal Squamous cell Carcinoma, with the hope to provid the new theoretical basis for esophageal cancer prevention and control strategy.Materials and MethodsTwo squamous esophageal cell lines and a strain of normal esophageal epithelial cell lines were provided by Qianfoshan Hospital of Shandong University center lab. Esophageal squamous cell carcinoma and corresponding normal tissues of53patients were obtained from Department of Chest Surgery, Qianfoshan Hospital of Shandong University. The reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of Bmi-1and Mel-18in three strains of cell lines,cancer tissue and corresponding normal tissue in the53cases,then analyzed the association between their expression and the clinical parameters of the tumors (gender, tumor location, histological differentiation,invasive depth,clinical stage, lymph node metastases).The association between Bmi-1and Mel-18expression was also analyzed.Results1. The analysis revealed significantly overexpression of Bmi-1in2squamous esophageal cell lines and low expression of Mel-18in the2squamous esophageal cell lines.2. There was significantly increased expression of Bmi-1in carcinoma tissues than in corresponding normal tissues (P<0.05). The difference of expression in the groups with and without lymph node metastases was significant (P<0.05); The expression levels of Bmi-1were rose consequently in TNM stage Ⅰ, Ⅱ and Ⅲ/IVA(P<0.05);The expression in invasion fiber membrane group was significantly higher than that without invasion(P<0.05); There was no relation between Bmi-1expression and any clinicopathological parameters, such as gender,tumor location, histological differentiation (P>0.05).3. There was significantly decreased expression of Mel-18in carcinoma tissues than in corresponding normal tissues (P<0.05).There was no relation between Mel-18expression and any clinicopathological parameters, such as gender,tumor location, histological differentiation and invasive depth (P>0.05). The expression levels of Mel-18 in TNM stage Ⅰ, Ⅱ,Ⅲ/ⅣA were reduced consequently (P<0.05). The difference of expression in the groups with and without lymph node metastases was significant (P<0.05).4. The expression of Bmi-1is negatively correlated the expression of Mel-18(P<0.05).Conclusions1. The Bmi-1mRNA expression was significantly Overexpression in squamous esophageal cell.The Bmi-1mRNA expression levels was significantly higher in53carcinoma tissues than corresponding normal tissues. The mRNA expression of Mel-18was significantly low expression in squamous esophageal cell. The Mel-18mRNA expression levels was significantly lower in53carcinoma tissues than corresponding normal tissues. These results suggested that Bmi-1and Mel-18may play a important role in the progression of esophageal squamous cell carcinoma.2. The expression of Bmi-1and Mel-18in different TNM stages and lymph node metastasis group have significant difference,and the expressions of Bmi-1were positively correlated with the depth of tumor invasion, suggest the expression differences of Bmi-1and Mel-18and the tumor stage and lymph node status of esophageal squamous cell carcinoma are closely related.3. The expression of Bmi-1and Mel-18is a certain negative correlation, Bmi-1and Mel-18may have a mutual effect in the occurrence,development, invasion and metastasis of esophageal squamous cell carcinoma.4. It is possible that Mel-18could be used as a definite diagnosis and evaluating prognosis marker of Esophageal Squamous cell carcinoma.