Expression And Clinical Significance Of FBXW7, FAS And MCM7 In Colorectal Carcinoma

Background and objectivesColorectal cancer, With 655,000 deaths worldwide per year, it is the fourth most common form of cancer in the United states and the third leading cause of cancer-related death in the Western world. Certain factors increase a person's risk of developing the colotectal cancer, these include:1:age, The risk of developing colorectal cancer increases with age. Most cases occur in the 60s and 70s, while cases before age 50 are uncommon unless a family history of early colon cancer is present. 2:Polyps of the colon.3:Heredity.4:Smoking, An Amerrican cancer society study found "Women who smoked were more than 40% more likely to die from colorectal cancer than women who never had smoked. Male smokers had more than a 30% increase in risk of dying from the disease compared to men who never had smoked.5: Diet.6:Lithocholic acid, it acts as a detergent to solubilize fats for absorption.It has been implicated in human and experimental animal carcinogenesis.7:Physical inactivity.8:Viruses, such as HPV.9:Primary Sclerosing Cholangitis.10:Low levels of selenium.11:Inflammatory bowel disease, About one percent of colorectal cancer patients have a history of chronic ulcerative colitis.12:Environmental factors, the main factor is diet custom.13:Exogenous hormones, there is evidence that exogenous estrogens such as hormone replacement therapy (HRT), tamoxifen, or oral contraceptives might be associated with colorectal tumors.14:Alcohol.15:Vitamin B6, intake is inversely associated with the risk of colorectal cancer.16:History of cancer, Individuals who have previously been diagnosed and treated for colon cancer are at risk for developing colon cancer in the future. Women who have had cancer of the ovary, uterus, or breast are at higher risk of developing colorectal cancer.Colorectal cancer is a disease originating from the epithelial cells.lining the colon or rectum of the gastrointestinal tract, as a result of mutations along the Wnt signaling pathway. Some of the mutations are inherited, and others are acquired. There are at least two major different carcinogenic pathways in colorectal carcinoma. One is chromosomal instability pathway, follows by allelic losses on chromosome 5q (APC),17p (P53), and 18q(DCC/SMAD4).The other pathway is microsatellite instability, new research shows that it is in relation to the dificiency of repair gene hMLH1 or hMSH2, there are about 15%-20% sporadic colorectal carcinomas belong to this pathway.1 Materials and Methods1.1 A total of 110 resected colorectal cancer specimens were enrolled in the study during the period form january 2009 to february 2010 in the first affiliated hospital of Zhengzhou university,including 47 men and 63 women, with age ranging from 20-82 (average 54.2±13.6 years), and 56 tubular adenocarcinoma specimens,26 papilary adenocarcinoma specimens,21 mucinous adenocarcinoma specimens,7 signet-ring cell adenocarcinoma specimens.84 high-middle grade differentiation adenocarcinoma specimens,26 low grade differentiation adenocarcinoma specimens. Clinical staging was done according to Ducks method,3 patients with stage A,70 patients with stage B,20 patients with stage C,17 patients with stage D. And 24 cases of colorectal adenoma and 18 cases of para-carcinoma normal mucosa tissue were collected, and the distance from the tumor edge to normal tissue is≥7cm.1.2 Main reagent, FBXW7 mouse monoclonal antibody,MCM7 mouse monoclonal antiboday (Santa Cruz, USA), FAS rabbit polyclonal antibody (zhongshang goldbridge biotechnology company), S-P agent box and DAB agent(zhongshang goldbridge biotechnology company).1.3 Immuohistochemistry FBXW7, FAS, MCM7 were performed on cases using FBXW7 antibody at 1:60,FAS antibody at 1:80, MCM7 antibody at 1:100 respectively. and PBS was used as negative control.1.4 Statistical analysis SPSS 17.0 software was used for statistical analysis. Chi-square test was used to analyze the date.The correlation of FBXW7/FAS, FBXW7/MCM7, FAS/MCM7 was analyzed with Spearman rank correlation.Test leveα<0.05.2 Results2.1 the expression of FBXW7 in colorectal carcinoma, adenoma and normal tissue The expression rates of FBXW7 in colorectal carcinoma,adenoma and normal tissue are 58.2%,75.0%,88.9%,and the difference between colorectal carcinoma and normal mucosa tissue is statistically significant(P<0.05),which is significantly correlated with the differentiation of tissues, the metastasis of lymph node and the tumor size(P<0.05).2.2 the expression of FAS in colorectal carcinoma, adenoma and normal tissueThe expression rates of FAS in colorectal carcinoma,adenoma and normal tissue are 94.3%,75.0%,55.6%, the difference between colorectal carcinoma and normal mucosa tissue is statistically significant(P<0.05),and which is significantly correlated with the age(P<0.05)2.3 the expression of MCM7 in colorectal carcinoma, adenoma and normal tissueThe expression rates of MCM7 in colorectal carcinoma,adenoma and normal tissue are 95.8%,66.7%,22.2%.There are 29.2% positive staining,39.1% strong positive staining were found in colorectal carcinoma,and the difference among three groups is statistically significant (P<0.05)2.4 the correlations among FBXW7,FAS and MCM7There is a negative correlation between FBXW7 and FAS, MCM7 (P<0.05). There is a positive correlation between FAS and MCM7(P<0.05) in colorectal carcinoma.3 Conclusions3.1 FBXW7 might be new markers in prediction for colorectal carcinoma, and new therapeutic targets for colorectal carcinoma.3.2 FAS may plays roles in cell proliferation and early diagnosis of colorectal carcinoma.3.3 MCM7 may plays important roles in cell proliferation.