The Significance Of Runx3Expression In Colorectal Cancer And Adenoma And Its Correlation With Survivin And Ki-67

This study detected the expression of RUNX3, Survivin and ki-67respectively and their correlation, and then relationship between their expression and the biological behavior of colorectal tumor. We were to determine whether they could be used as molecular markers for early diagnosis of gastrointestinal cancer. Finally, we explored the expression of RUNX3, Survivin and ki-67in the colorectal adenomas-cancer process, and tried to study their roles in the occurrence, development, invasion, metastasis and prognosis of colorectal tumor so as to provide more information for the early diagnosis and clinical treatment. Understanding of the relationship of RUNX3, Survivin and ki-67in the colorectal adenoma-carcinoma process, we might find new therapeutic targets and experimental basis for gastrointestinal tumors.We collected Formalin Fixed Paraffin Embedded tissues from June,2011to February,2012in the First Affiliated Hospital of Hebei North University. There were60cases of colorectal adenomas with37Low-grade dysplasia and23severe-grade dysplasia,60cases of colorectal cancer, all without preoperative radiotherapy and chemotherapy, and30cases of colorectal normal mucosa as controls. We stained RUNX3, Survivin and ki-67proteins by immunohistochemical and detected RUNX3mRNA and SurvivinmRNA by in situ hybridization. We observed the staining results with an optical microscope. Image analysis based on the need for staining results. Comprehensive analysis of their correlation with the clinicopathological factors (age, gender, tumor size, location, depth of invasion, differentiation, TNM stage and lymph node metastasis) was carried out by SPSS17.0statistical packageThe positive rate of RUNX3, Survivin and ki-67protein in colorectal cancer was38.33%(23/60),73.33%(44/60),80.00%(48/60) respectively,in colorectal adenomas associated with severe-grade dysplasia was43.48%(10/23),52.17%(12/23),65.21%(15/23) and in colorectal adenomas associated with Low-grade dysplasia was72.97%(27/37),13.51%(5/37),21.62%(8/37) respectively, and in normal colorectal tissues was86.67%(26/30),10.00%(3/30),6.67%(2/30). RUNX3protein expression decreased gradually in the adjacent normal tissue, adenoma with low grade dysplasia, adenoma with severe dysplasia and colorectal cancer tissues. RUNX3protein expression in cancer tissues was significantly lower than that in normal colorectal tissue and glandular tumor with low-grade dysplasia (P <0.05). On the contrary, Survivin and ki-67protein expression was gradually increased, and in severe dysplasia adenomas stage, their expression was significantly higher than that in normal tissue and low-grade dysplasia gland tumors (P<0.05).In the60cases of colorectal cancer specimens, there were23cases,44cases,48cases with RUNX3, Survivin and ki-67protein positive expression respectively. And among the23cases with RUNX3expression, there were11cases with Survivin positive expression and14cases with ki-67positive expression. Correlation analysis by Spearman showed RUNX3and Survivin or RUNX3and ki-67were significant negative correlated, whereas Survivin and ki-67expression presented a significant positive correlation.The positive expression rate of he RUNX3and Survivin mRNA in colorectal cancer, adjacent normal tissue, adenoma with low to moderate dysplasia and adenoma with severe dysplasia was40.00%and76.67%,90.00%and6.67%,78.38%and10.81%,43.48%and56.52%, respectively and the difference was statistically significant (P<0.05). The RUNX3and Survivin protein expression in60cases of cancer tissue samples was23 cases and44cases, while RUNX3and Survivin mRNA expression was24cases and46cases respectively. Whereas in the30cases of normal colorectal mucosal tissue,26cases expressed RUNX3protein, only three cases with Survivin protein expression, and RUNX3mRNA expressed in27cases, only two cases with Survivin mRNA expression. From the adjacent normal tissue to the colorectal cancer tissue, RUNX3expression gradually reduced, while the expression of Survivin gradually increased, and the difference was statistically significant.RUNX3expression was negatively correlated with TNM stage, depth of invasion, lymph node metastasis, liver metastasis in patients with colorectal cancer (P<0.05) but wasn’t correlated with gender, age, tumor size, location, degree of differentiation and histological type (P>0.05). Survivin expression was positively correlated with TNM stage, depth of invasion, lymph node metastasis, liver metastasis in patients with colorectal cancer (P<0.05).The change of Runx3and Survivin expression level was early molecular events in the adenoma-carcinoma model development process. Runx3inactivation and Survivin gene activation both occurred in adenoma stage. RUNX3, Survivin, Ki-67protein were correlated with the degree of differentiation, depth of invasion, TNM stage and lymph node metastasis in colorectal cancer. The expression of RUNX3and Survivin is high consistent in the two detection methods of the immunohistochemistry and in situ hybridization.RUNX3and ki-67or RUNX3and Survivin expression was negatively related in colorectal cancer tissue; Taking a joint detection of RUNX3, Survivin and ki-67was a recommended way to screen early tumors, to predict tumor early transfer, and to assess the prognosis. Also it could provide valuable biological factors for colorectal cancer early intervention.Runx3might become a new target for colorectal cancer targeted therapy. In-depth study of the relationship between the three might find more significant value in early detection and prevention of colorectal cancer in the future.