Expression And Prognostic Significance Of Guanine Nucleotide Exchange Factor In Rhabdomyosarcoma

Purpose: Based on the array comparative genomic hybridization (aCGH) study, to detect the expressionof guanine nucleotide exchange factor T (GEFT) protein in RMS and its clinic pathological significance forRMS, which aims to lay a foundation for further elucidating the molecular mechanism, moleculardiagnosis and targeted therapy of RMS.Methods: We investigated guanine nucleotide exchange factor, GEFT, at expression level in45patientswith rhabdomyosarcoma (23cases of embryonal rhabdomyosarcoma,20cases of alveolarrhabdomyosarcoma and2cases of pleomorphic rhabdomyosarcoma) and36cases of normal striatedmuscle controls using immunohistochemistry using tissue microarrays. Correlation of these expression andclinicopathological factors with prognosis of RMS was analyzed by SPSS17.0.Results:(1) The expression rate of GEFT in RMS samples (42/45,93.33%) was significantly higher (P<0.05) than that in normal controls (5/36,13.89%). Moreover, the overexpression rate of GEFT in RMS(31/45,68.89%) was also significantly higher (P <0.05) than that in normal controls (0/36,0.00%).(2)The normal striated cell of GEFT protein expression mainly distributed in cytoplasm, the cells of RMSmainly in the nucleus, cytoplasm was also expressed, and in the poorer differentiated RMS, the moresignificant nuclear expression(PRMS <ERMS <ARMS).(3) Increased expression of GEFT correlatedsignificantly with advanced disease stages (stages III/IV)(P=0.001), lymph node metastasis (P=0.019),and distant metastasis (P=0.004), respectively, in RMS patients.(4) Kaplan-Meier survival analysisshowed that, median survival time (50.00months) of patients with GEFT protein weakly positiveexpression was significantly longer than that (26.00months) of patients with overexpression. RMS patientshaving overexpressed GEFT experienced worse overall survival (OS) than those having low levels ofGEFT (Log-rank，χ2=11.676, P=0.001).(5) The Cox regression model analysis suggested: GEFToverexpression was determined to be an independent prognostic factor for poor OS in RMS patients(hazard ratio:3.491,95%confidence interval:1.121–10.871, P=0.004).Conclusions:(1) GEFT is highly expressed in RMS and its correlations with disease aggressiveness andmetastasis.(2) These findings suggest that GEFT may serve as a promising biomarker predicting poorprognosis in RMS patients, thus implying its potential as a therapeutic target.