Expression Of EIF-5A2 Protein In Human Brain Glioma

BackgroundGlioma is the most common primary intracranial tumor, which takes up about 35.26%—60.96% in all kinds of brain tumors. The major therapy methed of qlivwa is surgical operation. However, because of the infiltrative growth of the tumor, it's difficult to be resected completely; the tumor is easy to recur after surgery. Therefore, the pathogenesis, pathology and comprehensive therapy of glioma have always being an investigative issue for neurosurgeons. In addition, recurrence and metastasis of glioma, are hot topics that are needed to be solved. Moreover, searching for the invasiveness metastasis related specific gene and providing early diagnosis and therapy are the keys for decreate recurrence and cucveate survival rate. Evidences provided by recent cytogenetical studies demonstrated that there are high-frequency amplifications of chromosome 3q or partly 3q region in malignant epithelial tumors deriving from head and neck, esophagus, breast, gastrointestine and bladder. It indicates that chromosome 3q may contain single or multiple key oncogenes in certain DNA amplification region. Amplification and irregular expression may play an important role in tumor generation. In 2001, Guan et.al cloned a new candidate oncogene EIF-5A2 from 3q26.2 overamplification region in ovarian cancer cell via employing chromosome microdissection and screen- hybridization technique. EIF-5A2 was named because the protein encoding by it has 82% homology with EIF-5A2 which is the eukaryon initiation factor Previous investigations indicate that EIF-5A gene plays an important role in cell generation and proliferation, When EIF-5A protein was inhibited in the ovarian epithelial cell of Chinese hamster, the generation and proliferation of the epithelial cell were also significantly inhibited, which may lead to cell apoptosis. Tumor promoting effect of EIF-5A2 has been proved in vivo and in vitro. EIF-5A2, a member of eukaryotic initiation factor family, presents weakly expression in normal testis and brain cell. And high expression in certain human cancer cell e.g. ovarian cancer and colon cancer. and the high expression is related to the tumors'clinical stages. It was reported that EIF-5A2 overexpression In glioma has not been found in domestic litevatual. EIF-5A2 is a new cancer qene found in human ovarian cancer cell, and EIF-5A2 protein is a conservative eukaryotic protein too. Once the protein is synthesized, its lysine would be catalyzed into 8- hydroxyl-2, 7, 10-triglycoleucine by Deoxyhypusine Synthase (DHPS, Ne- lysine synthase), and activate EIF-5A2, which may maintain cell normal proliferation. Normal cell cycle would be delayed if DHPS activity was inhibited.Both protein and mRNA of EIF-5A2 express in either normal tissues or tumor cells, and they always overexpress in cells of certain malignant tumors such as ovarian cancer, esophagus cancer and colorectal cancer. It indicates that EIF-5A2 has a characteristic of tumor specificity expression; evidences provided by in vivo and in vitro demonstrate that EIF-5A2 has a promoting effect on tumor proliferation. Our investigation suggested that DHPS suppression affects proliferation of vascular endothelial cell and vasculogenesis, Abnormal DHPS-EIF-5A2 pathway activating is related to tumor metastasis, and affect generation and development of tumor via promoting tumor vasculogenesis.ObjectiveThe effects of EIF-5A2 protein on generation and development of glioma were investigated.Methods1. Tested the qualitative expression of EIF-5A2 protein in 54 cases of glioma and 6 normal brain tissues by Immunohistochemistry.2. Tested the semiquantitative expression of EIF-5A2 protein in 20 cases of glioma and 2 normal brain tissues by Western Blot. Results1. EIF-5A2 protein had overexpression in 54 cases of glioma. EIF-5A2 is brown yellow graininess and locates in cytoplasm mostly. It had no expressions in 6 normal brain tissues, and its positive rate in normal brain tissue and glioma were 0.0% (0/6) and 72.2% (39/54) respectively, which had statistical significance (P<0.01);2. We divided 54 cases of glioma into four groups according to I, II, III and IV levels set by WHO. EIF-5A2 protein positive rate in lower-level (I, II) and higher-level (III, IV) were 52.4% (11/21) and 84.8% (28/33) respectively, which had statistical significance (P<0.01);3. We had positive semiquantitative expression in 20 cases of glioma, Nevertheless, it had no expression in normal brain tissue.4. EIF-5A2 expression was unrelated to patients'age and sex.ConclusionEIF-5A2 has overexpression in glioma, while having no expression in normal brain tissue. It has statistical significance. In addition, its expression rises along with the enhancement of grade malignancy of glioma. It suggests that EIF-5A2 may play a role in tumor generation. However, it may be a new target for pharmacotherapy on glioma in the future.