Expression And Significance Of Histone H3K27 Demethylases JMJD3 In Oligodendroglioma

【Background】 Histones(H), as the major proteins constituents of the chromoctin, are not only a DNA supports, but also play critical roles in geneexpression and genomic imprinting and other aspects. There are many types of histone post-translational modifications, including acetylation, ubiquitination, methylation. The study of histone methylation becomes currently one of the most important research fields. More and more evidences proved that histone methylation dysfunction was closely related with tumorigenesis and development, and this methylation process is reversible. The further research of histone methylation will not only contribute to understanding of gene expression regulation, genetic and physiological mechanisms, but also for the diagnosis of cancer and other major diseases, prevention and prognosis. It has been found for a long time that histone acetylation, phosphorylation process is reversible, but never has found histone demethylase, so histone methylation was once considered to be stable and irreversible epigenetic modification process. Until histone lysine demethylase(lysine specific demethylase 1, LSD1) and peptide-based enzyme arginine(peptidylarginine deiminase 4, PAD4) were discovered in 2004, it was also confirmed that histone methylation and histone acetylation, phosphorylation, etc. is reversible, which also has opened up many new ideas in histone demethylase research field. JMJD3(jumonji domain-containing protein 3) is H3K27 me2/me3 histone demethylase, are considered to be related with epidermal nerve and immune cell development, and is also closely related with the transcription and chromatin activation also has significant relevance. Currently, there are few studies about the association between tumor and JMJD3. Therefore, this study analyzed the correlation of oligodendroglioma and JMJD3 for further revealing the role of JMJD3 in oligodendroglioma carcinogenesis mechanism.【Objective】 To explore the expression of histone demethylase JMJD3(jumonji domain-containing protein 3) in different tumor type, and the expression of JMJD3 in oligodendroglioma and glioblastoma specifically, and to analyze the correlation of expression of histone demethylase JMJD3 and the survival of patients with oligodendroglioma.【Methods】 1、By using tissue microarray screening and immunohistochemical staining, we screened out tumor tissue types with JMJD3 positive expression and compared with the corresponding normal tissues, and then choosed 50 cases of glioblastoma and oligodedroglioma and 39 cases of adjacent normal samples.2、Immunohistochemical SP method was used to detect the expression of JMJD3 in tissue microarray and tumor tissues and the corresponding normal tissues.3、Statistics was done with SPSS 13.0 software. 【Results】1、By using tissue microarray screening, we found that JMJD3 has been expressed in the nucleolus of normal oligodendrocytesbut negative in the oligodendroglioma.6 in 72 tissues were positive,and the rest of the tissues were negative(66/72). JMJD3 were also positive in E7(lung)、E9(lung)、G7(liver).2、In 50 cases paraffin specimens of glioma patients, 15 cases of tumor tissue were positive for JMJD3 protein; 39 cases of tumor adjacent tissues were positive, the others have no tumor adjacent tissues. In 20 cases of oligodendroglioma WHO II grade cases, the tumor cells in 6 cases were positive, the positive rate was 30%; 14 cases of tumor adjacent tissues were positive, the other six cases have no tumor adjacent tissues. Among 20 cases of oligodendroglioma WHO III grade cases, the tumor cells in 7 cases were positive, the positive rate is 35%; 18 cases of tumor adjacent tissues were positive, the other two have no tumor adjacent tissues. In 10 cases of WHO IV grade glioblastoma, the tumor cells were positive in two cases, the positive rate was 20%; tumor adjacent tissues of 7 cases were positive, the other three cases don’t have tumor adjacent tissues. In 40 cases of oligodendroglioma and anaplastic oligodendroglioma patients, 7 patients(17.5%) survive less than or equal to 22 months,the tumor cells of 1 case were positive(14.3%);23(57.5%) patients survive greater than 22 months, the tumor cells of 11 cases were positive(47.8%)(P=0.037); 10 cases(25%) patients were lost of follow-up. In 10 cases of glioblastoma patients, 3 patients(30%) survive less than or equal to 22 months, none of them had a positive tumor cells(0%); 3 patients(30%) survive greater than 22 months, the tumor cells of 2 cases were positive(66.6%); another 4 cases(40 %) were lost of follow up(P=0.013).【Conclusion】1、JMJD3 was expressed in the normal oligodendrocytes in alls the detected cases, loss of JMJD3 expression is frequent in oligodendroglioma and glioblastoma.2、The patients with JMJD3 positivity survive longer than that with JMJD3 negativesignificantly. The data suggesting loss of JMJD3 protein may play an important role in the tumorigenesis and progression of oligodedrogiloma, JMJD3 may be a tumor suppressor gene.