Expression Characteristics And Clinical Significance Of RUNX3 In Glioma

Backgrounds and Objectives:Glioma is the most common malignancy of primary malignant tumor in the central nervous system, with high morbidity of 35-60% among intracranial tumours. Glioma appears unfavourable prognosis and high mortality because of its dangerous location, difficulty of total resection and poor curative effect of chemo and radiotherapy. Abnormal activation of oncogene and inactivation of anti-oncogene relate to the tumor formation of glioma. The exact mechanism of glioma is still unclear, and the lackage of accurate and effective method for early diagnosis is the main cause to induce the high mortality. Therefore, exploration of genetic alterations closely linked with glioma formation and dissemination would be of great values in prevention, early detection, prognostic evaluation and prolongation live time of this malignancy.RUNX3, members of runt structural domain transcription factor family, is one of the newly found anti-oncogene that has been known to participate in the carcinogenesis and development of nervous system and immune function. It is the hotspot focused by researchers for the transcriptional controlling in cell proliferation and apoptosis. It has been well documented down-regulated expression and poor prognosis in digestive tumors of gastric, esophageal, colorectal cancer, and digestive glands tumors of hepatic, pancreatic cancers and others including lung, mammary cancer and leukemia. The loss of RUNX3 protein depends on the hyper methylation of DNA promoter region and genetic heterozygosis deletion. But there is few corresponding study on glioma.Based on the above unclear issues, the current study aimed to profile expression of RUNX3 during stepwise glioma carcinogenesis and to analyze the relationship to the series of pathological factors through the methods of tissue array and immunohistochemistry staining, the purpose of which is to provide valuable experimental evidences in early diagnosis, prognostic evaluation and index screening of gene therapy.Materials and Methods:Glioma and relative normal brain tissues were all selected from the Anshan City Tumour Hospital. By the methods of paraffin embedded tissue array immuno-histochemistry, the expression pattern of RUNX3 in different glioma tissues were detacted, the correlation between RUNX3 expression and glioma pathology was analyzed. The data were statistically analyzed by Kruskal-Wallis, Mamm Whitney and Spearmen with SPSS 11.0 software.Results:1.94.7%(18/19,) of normal brain tissues express RUNX3 protein however 61.8%(34/55) gliom a showed down-regulation of RUNX3 expression, and statistical analyses with Kruskal-Wallis test and Mann-Whitney test revealed the significant differences between the two groups(P=0.000).2. No statistical differences could be observed in different gender, age group and different pathological gradings. Frequent loss of RUNX3 expression in larger tumors (25/33,75.6%) compared with that in smaller tumors (9/22,40.1%),significant difference could be established between the two groups (P=0.010). Down-regulation rate of RUNX3 expression in patients with live time less than 3 years was significant higher those of more than 3 years (79.2%,48.4%, p=0.021). Different pathological types of glioma appear different expression characteristics.55.8%,66.7% and 100% of astrocytoma, mesoglioma and the rest groups showed decreased protein expression. No expression differencecould be seen in the radiotherapy group and untreated group.Conclusion:1. The expression of RUNX3 gene is an important molecular event throughout the whole glioma carcinogenesis. The expression frequency decreases from noncancerous to tumor.2. The frequency of RUNX3 loss of larger tumors and shorter patients'live time is higher than that of smaller tumor and longer patients live time, but unrelated to factors of gender, age, grading. Different pathological types of glioma appear different expression characteristics.