Expression Characteristics And Clinical Significance Of RUNX3 In Colorectal Carcinoma

Backgrounds and Objectives:RUNX3 is one of tumor suppressor genes found in 1994 that has been recognized to belonging to transcription factor family of RUNX structural domain and participate in the development of nervous system, immune function and carcinogenesis. More and more researcher focus on the gene and proved that down-regulated expression in gastric cancer, esophageal carcinoma, hepatic cancer, pancreatic cancers lung cancer, mammary cancer and myelogenous leukemia compared with their relative normal tissues, which correlated whit differentiation level and prognosis. The loss of RUNX3 protein mainly depends on the epigenetic mechanism of methylation of DNA promoter region and genetic heterozygosis deletion.Colorectal carcinoma (CRC) is one of the commonest digestive cancers, which takes the third place of all the cancers among the world and has been the first morbidity diseases in developed countries such as Europe and America. In China the morbidity and mortality of CRC have increased rapidly current years and showed more youthful tendency. It has been demonstrated that the development of CRC is a multi-factors, multi-steps, internal and external inter-action results and the process including the cancer induction, cancer promotion and carcinogenesis and progression. Molecular pathological examination would be benefit for early diagnosis prognosis prediction and evaluation of sensitivity of chemoradiation therapy. Thus exploration of genetic and molecular alterations closely linked with colorectal carcinoma formation and dissemination would be of great values in cancer prevention, selection of individuational therapeutic schedule and prolong the patients survival time of this malignancy. There are more corresponding study on this fields.The current study aimed to profile expression of RUNX3 during stepwise CRC carcinogenesis and to analyze the relationship to the series of pathological factors through the methods of tissue array and immunohistochemistry staining (IHC), the purpose of which is to provide valuable experimental evidences in early diagnosis, prognostic evaluation and index screening of gene therapy of CRC.Materials and Methods:CRC and relative normal esophageal tissues were selected from the Xinhua affliated hospital of Dalian University from 2008-2011. All the samples were conclusively diagnosed without chemoradiotherapy. Adopting the methods of paraffin embedded tissue array, hematoxylin and eosin staining (H.E) and immunohisto- chemistry, the expression characteristics of RUNX3 in different colorectal tissues and the correlation with invasiveness and metastasis was analyzed. The data were statistically analyzed by SPSS 11.5 software.Results:1. Expression of RUNX3 in different colorectal tissues: The detection rate of RUNX3 protein in relative noncancerous tissues and cancer samples were 95.2% and 69.4%. Statistical analyses revealed the decreasing tendency of RUNX3 during the stepwise carcinogenesis (p=0.017). There were no significant differences of RUNX3 expression between the tumor in colon and tomor in rectum (75.0%, 67.4%, p=0.573).2. The relationship of RUNX3 expression and the pathological factors: There were no significant gender, age, differentiation level, and tumor size difference in expression of this protein (p=0.627, p=0.487, p=0.805, p=0.436). There were significant differences in RUNX3 expression in different gross type. Down-regulation of RUNX3 was more frequent in ulcer type than in the protrude type. Among 25 and 37 cases of LN negative and positive group, the RUNX3 protein labeled rate were 84.0% and 59.5%. Down-regulation of RUNX3 expression in LN positive group was significantly higher than that in LN negative group (p=0.041). No difference of RUNX3 expression was observed between throughout-layer invasion group and muscular-layer invasion group, but no statistical significance (p=0.627).Conclusion:1. The down-regulated expression of RUNX3 protein is an important molecular event in colorectal carcinogenesis.2. The frequencies of RUNX3expression are unrelated to factors of gender, age, differentiation level and tumor size except the gross type. The ulcer type shows the lower protein expression level than the protrude type. RUNX3 expression in LN positive group was statistically significantly lower than that in LN negative group, which indicate that down-regulation of RUNX3 contributes to invasion and progression of colorectal cancer, and is of important value in molecular diagnosis and prognosis prediction.