title: A three-gene signature and clinical outcome in esophageal squamous cell carcinoma.
abstract: It is increasingly apparent that cancer development depends not only on genetic alterations, but also on epigenetic changes involving histone modifications. GASC1, member of the histone demethylases affecting heterochromatin formation and transcriptional repression, has been found to be dysregulation in many types of cancers including breast cancer, prostate cancer, metastatic lung sarcomatoid carcinoma, and leukemia. In this study, we examined the expression of GASC1 and certain GASC1-targeted genes (KLF4, MYC, SOX2, PPARG, MDM2, and NANOG) and identified a three-gene prognostic signature (PPARG, MDM2, and NANOG), using risk scores based on immunohistochemical analyses of 149 tumor specimens from patients with esophageal squamous cell carcinoma (ESCC). The presence of a high-risk three-gene signature in the ESCC tumors was significantly associated with decreased overall survival (OS) of the patients. We validated the predictive value of the three-gene signature in a second independent cohort of 101 patients with ESCC in order to determine whether it had predictive value. The results were similar to those in 149 patients. According to multivariate Cox proportional hazards analyses, the predictive model of a three-gene signature was an independent predictor for OS (p = 0.005 in cohort 1, p = 0.025 in cohort 2). In addition, ROC analysis indicated that the predictive ability of the three-gene model was more robust than that of a single biomarker. Therefore, our three-gene signature is closely associated with OS among patients with ESCC and may serve as a predictor for the poor prognosis of ESCC patients.
authors.affiliation: Institute of Oncologic Pathology, The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, Guangdong, China; Department of Pathology, Shaoyang Central Hospital, Affiliated Shaoyang Hospital of University of South China, Shaoyang, Hunan, China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Sun
authors.forename: Jian-Yi
authors.initials: JY
authors.lastname: Wu
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Wu
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Shen
authors.forename: Xiu-E
authors.initials: XE
authors.lastname: Xu
authors.forename: Bo
authors.initials: B
authors.lastname: Chen
authors.forename: Shao-Hong
authors.initials: SH
authors.lastname: Wang
authors.forename: En-Min
authors.initials: EM
authors.lastname: Li
authors.forename: Li-Yan
authors.initials: LY
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics; D000090062:Kruppel-Like Factor 4; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D014408:Biomarkers, Tumor; C413655:KDM4C protein, human; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D056484:Jumonji Domain-Containing Histone Demethylases
keywords: esophageal squamous cell carcinoma; gene prognostic signature; histone demethylase; histopathology