Ziying Zhang1, Peng Chen2, Hui Xie3, Peiguo Cao1. 1. Department of Oncology, Third Xiangya Hospital, Central South University, Changsha, China. 2. Department of Urology, Xiangya Hospital, Central South University, Changsha, China. 3. Department of Thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha, China.
Abstract
PURPOSE: Our research was aimed to identify the expression, clinical value and biological significance of GINS complex subunit 4 (GINS4) in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: GINS4 was initially screened through weighted gene co-expression network analysis (WGCNA). The TCGA, GEO, and TIMER databases were applied for analyzing the GINS4 mRNA expression in HCC. GINS4 protein levels were detected via immunohistochemistry (IHC). Receiver operating characteristic (ROC) curve was applied for estimating the diagnostic significance of GINS4 in HCC. Kaplan-Meier plots, Cox model, and nomogram were used to assess the prognostic performance of GINS4 in HCC. Nomogram validation was conducted through time-dependent ROC and decision curve analysis (DCA). The Wanderer, UALCAN, and DiseaseMeth databases were utilized to identify GINS4 methylation levels in HCC. Genes co-expressed with GINS4 in HCC were estimated through the TCGA, cBioPortal, and GEPIA. GO, KEGG, and GSEA unraveled the possible biological mechanisms of GINS4 in HCC. RESULTS: WGCNA confirmed that GINS4 was one of hub genes significantly associated with histological grade of HCC. Multiple databases confirmed the significant upregulation of GINS4 in HCC tissues compared with non-tumor controls. IHC analysis of 35 HCC patients demonstrated that overexpressed GINS4 positively correlated with advanced TNM stage and poor pathological differentiation. GINS4 could effectively differentiate HCC cases from healthy individuals, with an AUC of 0.865. Increased GINS4 expression predicted unsatisfactory prognosis in HCC patients, especially in age >60 years, histological grade 1, HBV infection-negative, and occurring relapse subgroup. Nomogram incorporating GINS4 level and TNM stage displayed satisfactory predictive accuracy and clinical utility in predicting HCC prognosis. Upregulated GINS4 exhibited hypomethylated levels in HCC. Functional analysis indicated that GINS4 potentially positively modulated cell cycle and PI3K/AKT/mTOR pathway. CONCLUSION: GINS4 is overexpressed in HCC and is correlated with undesirable survival of HCC patients.
PURPOSE: Our research was aimed to identify the expression, clinical value and biological significance of GINS complex subunit 4 (GINS4) in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: GINS4 was initially screened through weighted gene co-expression network analysis (WGCNA). The TCGA, GEO, and TIMER databases were applied for analyzing the GINS4 mRNA expression in HCC. GINS4 protein levels were detected via immunohistochemistry (IHC). Receiver operating characteristic (ROC) curve was applied for estimating the diagnostic significance of GINS4 in HCC. Kaplan-Meier plots, Cox model, and nomogram were used to assess the prognostic performance of GINS4 in HCC. Nomogram validation was conducted through time-dependent ROC and decision curve analysis (DCA). The Wanderer, UALCAN, and DiseaseMeth databases were utilized to identify GINS4 methylation levels in HCC. Genes co-expressed with GINS4 in HCC were estimated through the TCGA, cBioPortal, and GEPIA. GO, KEGG, and GSEA unraveled the possible biological mechanisms of GINS4 in HCC. RESULTS: WGCNA confirmed that GINS4 was one of hub genes significantly associated with histological grade of HCC. Multiple databases confirmed the significant upregulation of GINS4 in HCC tissues compared with non-tumor controls. IHC analysis of 35 HCC patients demonstrated that overexpressed GINS4 positively correlated with advanced TNM stage and poor pathological differentiation. GINS4 could effectively differentiate HCC cases from healthy individuals, with an AUC of 0.865. Increased GINS4 expression predicted unsatisfactory prognosis in HCC patients, especially in age >60 years, histological grade 1, HBV infection-negative, and occurring relapse subgroup. Nomogram incorporating GINS4 level and TNM stage displayed satisfactory predictive accuracy and clinical utility in predicting HCC prognosis. Upregulated GINS4 exhibited hypomethylated levels in HCC. Functional analysis indicated that GINS4 potentially positively modulated cell cycle and PI3K/AKT/mTOR pathway. CONCLUSION: GINS4 is overexpressed in HCC and is correlated with undesirable survival of HCC patients.
Authors: Christopher E Barbieri; Eugene K Cha; Thomas F Chromecki; Allison Dunning; Yair Lotan; Robert S Svatek; Douglas S Scherr; Pierre I Karakiewicz; Maxine Sun; Madhu Mazumdar; Shahrokh F Shariat Journal: BJU Int Date: 2011-08-18 Impact factor: 5.588
Authors: Frank Jühling; Nourdine Hamdane; Emilie Crouchet; Shen Li; Bryan C Fuchs; Thomas F Baumert; Houssein El Saghire; Atish Mukherji; Naoto Fujiwara; Marine A Oudot; Christine Thumann; Antonio Saviano; Armando Andres Roca Suarez; Kaku Goto; Ricard Masia; Mozhdeh Sojoodi; Gunisha Arora; Hiroshi Aikata; Atsushi Ono; Parissa Tabrizian; Myron Schwartz; Stephen J Polyak; Irwin Davidson; Christian Schmidl; Christoph Bock; Catherine Schuster; Kazuaki Chayama; Patrick Pessaux; Kenneth K Tanabe; Yujin Hoshida; Mirjam B Zeisel; François Ht Duong Journal: Gut Date: 2020-03-26 Impact factor: 23.059