title: EGFR and SYNE2 are associated with p21 expression and SYNE2 variants predict post-operative clinical outcomes in HBV-related hepatocellular carcinoma.
abstract: This study was to explore the association between gene variants and p21 expression and investigate the TP53-independent p21 regulation in hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) patients from Guangxi by genome-wide association study. 426 HBV-related HCC patients were enrolled. Results showed that, after quality control, a total of 21,643 SNPs were identified in 107 p21 positive and 298 p21 negative patients. The variants of epidermal growth factor receptor (EGFR; rs2227983 and rs6950826) and spectrin repeat containing, nuclear envelope 2 (SYNE2; rs8010699, rs4027405 and rs1890908) were associated with p21 expression. Moreover the haplotype block (rs2227983 and rs6950826, r(2) = 0.378) in EGFR and the haplotype block in SYNE2 (rs8010699 was in strong LD with rs4027405 and rs1890908 (r(2) = 0.91 and 0.70, respectively)) were identified, and the haplotype A-G of EGFR and haplotype G-A-A of SYNE2 were significantly associated with p21 expression (P < 0.01). rs4027405 and rs1890908 were significantly associated with overall survival, and patients with AG/GG genotypes of SYNE2 gene had a worse overall survival (P = 0.001, P = 0.002). Our findings indicate that variants of EGFR and SYNE2 play an important role in p21 regulation and are associated with the clinical outcome of HBV-related HCC in a TP53-indenpdent manner.
authors: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Chuangye
authors: C
authors: Han
authors: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Xiwen
authors: X
authors: Liao
authors: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Wei
authors: W
authors: Qin
authors: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Long
authors: L
authors: Yu
authors: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Xiaoguang
authors: X
authors: Liu
authors: Department of Pathology, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Gang
authors: G
authors: Chen
authors: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Zhengtao
authors: Z
authors: Liu
authors: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Sicong
authors: S
authors: Lu
authors: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Zhiwei
authors: Z
authors: Chen
authors: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Hao
authors: H
authors: Su
authors: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Guangzhi
authors: G
authors: Zhu
authors: Department of Pathology, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Zili
authors: Z
authors: Lu
authors: Department of General Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Zhiming
authors: Z
authors: Liu
authors: Department of Clinical Laboratory, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Xue
authors: X
authors: Qin
authors: Department of Clinical laboratory center, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Ying
authors: Y
authors: Gui
authors: Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Zengnan
authors: Z
authors: Mo
authors: Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Lequn
authors: L
authors: Li
authors: Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors: Tao
authors: T
authors: Peng
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000821:virology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006509:Hepatitis B / Q000150:complications*; D006515:Hepatitis B virus; D006801:Humans; D053208:Kaplan-Meier Estimate; D015810:Linkage Disequilibrium; D008113:Liver Neoplasms / Q000235:genetics* / Q000821:virology; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D011786:Quality Control; D012333:RNA, Messenger / Q000378:metabolism; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53
chemical_list: D014408:Biomarkers, Tumor; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; C485904:SYNE2 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; D066246:ErbB Receptors