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Study Of P190-B RhoGAP On Clinicopathologic Features And Prognosis In Patients With Non-Small Cell Lung Cancer

Posted on:2010-05-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:C WangFull Text:PDF
GTID:1114360302984852Subject:Surgery
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Objectives:Lung cancer is the leading cause of cancer deaths in humanbeing throughout the world, and the incidence is still increasing. Today,no useful biomark exists for detection of lung cancer. However, use of tumor marker for detection and treatment of lung cancer is promising. p190-B RhoGAP(a GTPase activating protein of 190kDa) is belong to Rho subfamily of Ras superfamily and can regulate actin cytoskeleton reorganization, leading to the appearance of aggregates of actin filaments, impacting cell growth, proliferation and aversion. Although emering evidence suggests that p190-B RhoGAP is causally involved in cancer formation and progression, like breast cancer, glioma and colorectal cancer, little is known about its significance in non-small cell lung cancer(NSCLC).The objective of present study was firstly to investigate the p190-B RhoGAP expression in clinical samples of NSCLC.Methods:We retrospectively reviewed the records and collected the medical datas of 160 patients who underwent a radical lobes resection for NSCLC. The expression levels and associativity with clinicopathologic characteristics of p190-B RhoGAP were analyzed with immunohistochemistry in tissue microassarys(TMAs). p190-B RhoGAP mRNA expression was measured by quantitative RT-PCR in another independent set of 30 patients. The mRNA expression level of p190-B RhoGAP was compared with the protein expression level in 20 of 30 patients.Results:p190-B RhoGAP was shown to be overexpressed in 43.75% NSCLC samples (p=0.003) and more located in cytoplasm. The expression of p190-B RhoGAP was significantly correlated with the stage of clinicopathology(p=0.018), histologic differentiation(p=0.047) and prognosis;it is a self-sustainingly prognosis factor. Compared with 57 months span in low expressed ones, the patiens with increased p190-B RhoGAP expression was associated with poor survival of NSCLC(only 40.59months); log-rank test showed a significant meaning in statistic (p=0.015).p190-B RhoGAPmRNA expression level in the tumor was higher than that in the normal alveolar cell tissue in 70% of 30 patients. No correlation between p190-BRho GAP protein expression and mRNA expression was found in NSCLC (p=0.323).Conclusions:The expression of p190-B RhoGAP was significantly correlated with the stage, histologic differentiation and prognosis of NSCLC, the expressed higher in this carcinoma had associated with poor survival; p190-B RhoGAPmRNA was overexpression in NSCLC; p190-B RhoGAP may be a valuable tumor marker for NSCLC.
Keywords/Search Tags:p190-B RhoGAP, NSCLC, immunohistochemistry, RT-PCR, TMAs, Western Blot
PDF Full Text Request
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