title: Overexpression of GEFT, a Rho family guanine nucleotide exchange factor, predicts poor prognosis in patients with rhabdomyosarcoma.
abstract: Rhabdomyosarcoma (RMS) is one of the most common soft-tissue sarcomas in children and adolescents with poor prognosis. Yet, there is lack of effective prognostic biomarkers for RMS. The present study, therefore, aimed to explore potential biomarkers for RMS based on our previous findings using array comparative genomic hybridization. We investigated guanine nucleotide exchange factor, GEFT, at expression level in 45 RMS patients and 36 normal striated muscle controls using immunohistochemistry using tissue microarrays. 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%). Increased expression of GEFT correlated significantly 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. In addition, RMS patients having overexpressed GEFT experienced worse overall survival (OS) than those having low levels of GEFT (P=0.001). GEFT overexpression 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). In conclusion, these observations provide the first evidence of GEFT overexpression in RMS and its correlations with disease aggressiveness and metastasis. These findings suggest that GEFT may serve as a promising biomarker predicting poor prognosis in RMS patients, thus implying its potential as a therapeutic target.
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, Xinjiang 832002, China ; Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University and Chinese Ministry of Education Shihezi, Xinjiang 832002, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, Xinjiang 832002, China ; Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University and Chinese Ministry of Education Shihezi, Xinjiang 832002, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Preventive Medicine, Shihezi University School of Medicine Shihezi, Xinjiang 832002, China.
authors.forename: Shugang
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, Xinjiang 832002, China.
authors.forename: Hongan
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, Xinjiang 832002, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, Xinjiang 832002, China.
authors.forename: Yuwen
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, Xinjiang 832002, China.
authors.forename: Bingcheng
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, Xinjiang 832002, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Cui
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, Xinjiang 832002, China.
authors.forename: Yunzhao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, Xinjiang 832002, China ; Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University and Chinese Ministry of Education Shihezi, Xinjiang 832002, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shihezi University School of Medicine Shihezi, Xinjiang 832002, China ; Key Laboratories for Xinjiang Endemic and Ethnic Diseases, Shihezi University and Chinese Ministry of Education Shihezi, Xinjiang 832002, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012208:Rhabdomyosarcoma / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D064067:Rho Guanine Nucleotide Exchange Factors; D012983:Soft Tissue Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D015996:Survival Rate; D055815:Young Adult
chemical_list: C475063:ARHGEF25 protein, human; D014408:Biomarkers, Tumor; D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors
keywords: Rhabdomyosarcoma; guanine nucleotide exchange factor; overexpression; prognosis