The Expression Of CCN2 In Colorectal Cancer And Its Clinic Pathological Significance

BackgroundColorectal carcinoma (CRC) becomes more and more commonly seen and the death caused by it is increasing worldwide recently. And it about 940,000 colorectal carcinoma new cases increases all over the world every year. And it about 500,000 died of colorectal carcinoma. And CRC is one of the most common tumors in our nation. Therefore, in order to increase survival rate and improve life quality, searching for method of early diagnosis and treatment is of most importance. Recent development in tumor immunology and molecular biology has shed some light on the mechanism of the occurrence and transferring of the colorectal carcinoma,which provides basis to gene therapy. And the mechanism of the occurrence in CRC is a complex process,which connects with polygene and multistage accumulation. At present,the mechanism of the occurrence in CRC which connects with CCN2 ( connective tissue growth factor, CTGF)was scarcely reported. This study in order to confirm CCN2 is a oncogene In CRC and the metastasis of CRC, the expression of CCN2 is a common phenomenon. And the mechanism of the occurrence in CRC maybe connect with the Wnt/β-Catenin signal pathways.ObjectiveResearch the correlation of CCN2 expression in colorectal carcinoma with its clinical pathological parameters,and judge CCN2 whether it would not be a target to diagnose or evaluate the prognosis in CRC . Further, to research the correlation between CCN2 with APC protein of Wnt/β-Catenin signal pathways, and investigate the mechanism of the occurrence of CCN2 in colorectal cancer. It can offer a reference for the follow experimental research,and also can provide some theoretical basis which for preventive treatment and find a new therapy target for CRC.Methods1. Choice the cases and collect the clinical pathological data:collected 30 cases of each tissue, that were mucosa tissue of normal rectum, adenoma of colorectum, limitable colorectal carcinoma, metastatic colorectal carcinoma, adjacent noncancerous tissue, and distant metastasis tissue. And collected the clinic data, which include the preoperative level of CEA, whether recurrence or not and the time of recurrence, neoplasm phases, whether the surgical margin has neoplasm or not, the grates of APGBI and Cr-POSSUM marking system survival time and so on.2. Detect the expression of CCN2 and APC protein which is the principal protein APCof Wnt/β-Catenin signal pathways in all of the pathology specimens: adopt streptavidin-perosidase of immunohistochemistry(SP) to assess the expression of CCN2(Zymed company immunohistochemical kit).Consult Fromowitz standard for evaluation to assess the percentage of positive cells. And according to dyeing of majority positive cells for scoring , Plus above-mentioned items. Protein intensity show negative mark 1, weakly positive mark 2, secondary positive mark 3, and strongly positive mark 4, specimen was aquadruplicate. Two pathologist view results with double-blind study, calculate and use the mean.3. Apply the spss16.0 statistical software to statistical analysis: use Kaplan-Meier survival analysis and univariate cox proportional harzards model, evaluate the dangerous individual variable in recrudescent CRC. Analysis the relationship of CCN2 with characteristic in clinical pathology. Expect the express level of CCN2, also conclude the level of CEA, diameter of neoplasm, neoplasm staging, and situation of surgical margin. P<0.05 be considered had statistical significance. Fourfold table data useχ~2 test, if the theoretical frequency less-than 5 or total cases less-than 40, should useχ~2 test adjustment or Fisher exact propability.ResultsImmunohistochemiscal S-P method:(1) In this experiment(table 1 and table 3)show that, CCN2 protein were high-expression in limitable colorectal carcinoma, metastatic colorectal carcinoma, and distant metastasis tissue, respectively 76.67%,73.33% and 70.00%. And adjacent noncancerous tissue, adenoma of colorectum, mucosa tissue of normal rectum were low-expression(respectively 6.67%,23.33% and 0.00%).χ~2=74.263,P=0.000,the discrepancy was considered had statistical significance.(2) APC protein were low-expression in limitable colorectal carcinoma, metastatic colorectal carcinoma, and distant metastasis tissue, respectively 26.67%,23.33% and 16.67%. In adjacent noncancerous tissue, adenoma of colorectum, mucosa tissue of normal rectum were high-expression(respectively 86.67%,76.67% and 90.00%).χ~2=70.00,P=0.000,the discrepancy was considered had statistical significance..(3) CCN2 expression was no significant correlation to age, sex, pathology typing tumor location (P> 0.05), but significant correlation with neoplasm phases , five-year survival rate, the preoperative level of CEA ,tumor differentiation, P<0.05 be considered had statistical significance(χ~2=4.689, P=0.03;χ~2=4.13, P=0.042). CCN2 express more strongly, neoplasm phases more advanced, and prognosis will get worse. So this result show that CCN2 may be one of oncogenes. Conclusion1. CCN2 gene maybe one of oncogenes, it's expression connection the clinical pathological parameters in colorectal cancer. So it can be considered as an effective indicator to diagnose CRC and as a factor for assessing its prognosis.2. In the occurrence mechanism of colorectal cancer,CCN2 may connect with APC protein of Wnt/β-Catenin signal pathways.3. This research can offer a reference for the follow zoopery and cells experimental research,and also provides some theoretical basis which for preventive treatment and find a new therapy target for CRC.