Expression Characteristics And Clinical Significance Of RUNX3 In Esophageal Cancers

Backgrounds and Objectives:Esophageal cancer (EC) is the high-morbidity malignancies in China taken the fourth location after lung cancer, hepatic cancer and gastric cancer. The exact mechanism of EC is still unclear and the lackage of accurate and effective method for early diagnosis is the main cause to induce the high mortality of EC. So far the principal treatment of EC is exairesis, but the unfavourable prognosis leads to about 10% of 5-year-life time after operation. Therefore, exploration of genetic alterations closely linked with EC formation and dissemination would be of great values in prevention, early detection and prognostic evaluation of this malignancy.Multiple oncogene activation and anti-oncogene inactivation have been known to participate in the complicated process of esophageal carcinogenesis, one of which is RUNX3, a newly known inactivated oncogene. RUNX3 belongs to the RUNX family that with three members including RUNX1, RUNX2 and RUNX3, that are relate to the human diseases. RUNX3 is the shortest gene in its family and takes part in the cytogene expression regulation in embryonic development. It has been reported that with the dedifferentiation of tumor cells, and disappearance of polarity, the disproportion expression of RUNX3 will induce the high infiltration tendency and high lymphatic metastasis of the cancer cells and poor prognosis. It is indicated that the disorder of RUNX3 might serves as a biological indicator of cell dedifferentiation and patients' poor prognosis. But there is few corresponding study on EC.Based on the above unclear issues, the current study aimed to profile expression of RUNX3 during stepwise esophageal carcinogenesis and to analyze the relationship to the series of pathological factors to build the foundation of EC early diagnose, prognosis evaluation and genetic therapy. Materials and Methods:EC, precancerous lesions and relative normal esophageal tissues were all selected from the Anshan City Tumour Hospital from 1999-2008. All the exairesis samples were conclusive diagnosed without chemoradiotherapy. By the methods of paraffin embedded tissue array immunohistochemistry, the expression pattern of RUNX3 in different esophageal tissues were detacted, the correlation between RUNX3 expression and EC invasiveness and metastasis was analyzed. The data were statistically analyzed by Kruskal-Wallis and Mamm Whitney with SPSS 11.0 software.Results:1.The expression rate of RUNX3 in noncancerous tissues, premalignant tissues and cancer samples were 77.8%,78.9% and 42.2%, statistical analyses with Kruskal-Wallis test and Mann-Whitney test revealed the increasing diminished tendency of RUNX3 during the stepwise esophageal carcinogenesis. There were significant differences of RUNX3 downregulation both between the EC group and noncancerous mucosa or premalignant lesions (p=0.043, p=0.000), but not between the ESCC and adencarcinoma group (p=0.297) and between noncancerous and premalignant epitheial(p=0.939).2. No statistical differences could be observed in different gender, age, differentiation level and tumor size group (p=0.800/0.166, p=0.448/0.070).3. Downregulation of RUNX3 expression was closely related to EC lymphatic metastasis, the RUNX3 expression in LN positive group was significantly less than that in LN negative group. Higher down-regulation rate of RUNX3 were observed both in LN positive group (p=0.000), T3,4 group (p=0.002) and theâ…¢-â…£stage (p=0.087).Conclusion:1. The expression of RUNX3 gene is an important molecular event throughout the whole esophageal tumorigenesis, development and dissemination. The expression frequency dncreases from noncancerous, precancerous and cancer epithelial, especially in adencarcinoma.2. The frequency of RUNX3 is unrelated to factors of gender, age, differentiation and tumor size. RUNX3 decreased expression in LN positive, T3,4 andâ…¢-â…£group that statistically significantly different from that in LN negative, T1,2 andâ… -â…¡groups, which indicate that RUNX3 contributes to invasion and progression of EC and is of important value in molecular diagnosis and prognosis prediction.