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FBXW7and Ki-67Expression In Human Glioma And Clinical Significance

Posted on:2014-01-10Degree:MasterType:Thesis
Country:ChinaCandidate:Z M WangFull Text:PDF
GTID:2234330398491706Subject:Surgery
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Purpose and background: Human glioma is the most common type oftumor in the central nervous system, accounting for50%and60%ofintracranial tumors, the5-year survival rate only20%to30%.Glioma cellswere invasive and expansive growth with the characteristics of a highincidence,high relapse rate, high mortality and low cure rate, serious harm tohuman health and quality of life. With the rapid development of modernneurosurgery scientific and medical engineering technology, and actively carryout the study of the pathogenesis of glioma, and with the help of modernmedical equipment and new diagnostic techniques, individual therapy, thediagnosis and treatment of glioma received considerable progress, and evenbreak some surgery "restricted area", and achieved gratifying results.Nevertheless, the final efficacy and prognosis of glioma patients there is nofundamental change, is still an important research topic in the field ofneuroscience.FBXW7is a tumor suppressor gene recently discovered, it’s transcriptFBXW7belongs to the F-box protein family, and is a target proteinrecognition subunit of the SCF ubiquitin ligase, plays an important role in theubiquitin-proteasome pathway. The substrates of FBXW7are mostlyoncogene products, such as c-Myc, c-Myb, Cyclin E, c-Jun, Notch, Aurora-A,etc.,and in breast cancer, ovarian cancer, endometrial cancer, colon cancer, bileduct cancer, gastric cancer, lung cancer, pancreatic cancer, prostate cancer andother human tumors were found the mutation of FBXW7.Ki-67is a proliferating cell nuclear antigen which located in the nucleusand its function is closely related to mitosis. Ki-67is expressed only in theperiodically hyperplasia nucleus but in other cells do not express, G0cellwithout this antigen. As an important marker of cell proliferation, Ki-67has been widely applied to the determination of tumor proliferative activity andclinical and basic research, is also an important factor affecting tumorprognosis.This experiment through detect the FBXW7and Ki-67gene and proteinexpression in the normal brain tissue and different grade glioma tissue,toexplore the relationship between FBXW7and Ki-67, the role of them in thetumorigenesis and development, the relationship between the clinical andpathological features, which will provide clues and basis for glioma diagnosisand treatment.Methods: Using immunohistochemistry(IHC,SP method) and real-timefluorescence quantitative PCR (RT-PCR) to detect the FBXW7and Ki-67expression in10cases normal human brain which come from intracranialdecompression due to trauma or cerebral hemorrhage and58cases gliomatissue that undergo surgical resection and pathologically confirmed, thestatistical analysis of the experimental data by the statistical softwareSPSS13.0. Using Kruskal-Wallis H test to compare the same indicatorsbetween different clinical pathological type,using the Spearman rankcorrelation analysis to explore the expression relationship between FBXW7and Ki-67. The inspection level a <0.05.Results:1IHC results: The expression of FBXW7and Ki-67are detected in thenormal brain tissue and glioma,FBXW7and Ki-67expression levels isstatistically significant in the three groups of normal brain tissue, low-gradegliomas and high-grade gliomas (P <0.001), FBXW7expression graduallydecreased with increasing degree of glioma malignance but Ki-67expressiongradually increased, FBXW7and Ki-67expression is negative correlation (r=-0.609, P=0.000).2RT-PCR results: FBXW7and Ki-67expression levels in the normalbrain tissue, low-grade gliomas and high-grade gliomas are statisticallysignificant (P <0.05), expression of the amount of FBXW7gradually reducedwith the degree of malignancy increased but Ki-67expression gradually increased, FBXW7and Ki-67expression is negatively correlated (r=-0.487,P=0.000). But FBXW7and Ki-67comparison between groups of normalbrain tissue and low-grade gliomas is not correlation (P=0.073) in the P<0.05level of inspection. Remaining comparisons between the two groups aresignificant differences.Conclusions:1FBXW7expression having a significant difference in normal braintissue and glioma, the highest level of expression is in the normal brain tissue,the expression level of FBXW7gradually decreased with the increased degreeof gliomas malignance.2Ki-67expression in normal brain tissue and glioma is significantdifferences, the lowest level of expression is in the normal brain tissue, withthe increased glioma degree, Ki-67expression level gradually rises, consistentwith the results both domestic and foreign reported before.3FBXW7and Ki-67expression in normal brain tissue and gliomashave a significant correlation,with the FBXW7expression level reduced,Ki-67expression level gradually increased.4In the course of gliomas occur, FBXW7lack of expression mayrelieve the inhibition of cell proliferation, thereby promoting tumor formation.FBXW7may become a new target for the treatment of glioma. DetectionFBXW7and Ki-67expression may helps determine the prognosis of gliomapatients to guide clinical treatment.
Keywords/Search Tags:FBXW7, Ki-67, glioma, immunohistochemistry, RT-PCR
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