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基于生物信息学分析和全基因组关联研究的肝细胞癌中NM23的临床意义及遗传因素

Clinical Implication and the Hereditary Factors of NM23 in Hepatocellular Carcinoma Based on Bioinformatics Analysis and Genome-Wide Association Study.

作者信息

Yang Chengkun, Han Chuangye, Wang Xiangkun, Liao Xiwen, Liu Xiaoguang, Qin Wei, Yu Long, Zhu Guangzhi, Su Hao, Lu Sicong, Chen Zhiwei, Yu Tingdong, Liu Zhen, Huang Ketuan, Liu Zhengtao, Liang Yu, Huang Jianlu, Peng Tao

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.

Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong Province, China.

出版信息

J Oncol. 2018 Dec 18;2018:6594169. doi: 10.1155/2018/6594169. eCollection 2018.

Abstract

NM23 expression is closely associated with hepatocellular carcinoma (HCC) recurrence, but the hereditary factors influencing NM23 levels are unknown. Using public database, the diagnostic value of in HCC was investigated. A total of 424 hepatitis B virus- (HBV-) related HCC patients were enrolled to perform a genome-wide association study for identifying candidate variants associated with NM23 expression level. Additionally, a logistic regression model, haplotypes, and survival analysis were performed in the subsequent analysis. We identified high NM23 expression levels that have a diagnostic accuracy in HCC tissues and had a poor recurrence-free survival in HBV-related HCC patients. Variants near Psoriasis susceptibility 1 candidate 1 () and StAR related lipid transdomain containing 3 () are associated with NM23 expression. The haplotype TGCACA and the haplotype GG have favorable cumulative effects on NM23 expression. Further, variants in PSORS1C1 were associated with either overall survival (rs556285588, rs3095301, and rs3131003) only or overall survival and recurrence-free survival (rs560052000 and rs541820233) both in HCC patients. Our findings suggested that variants at the and loci play an important role in regulation. Moreover, variants in are potential biomarkers for the prediction of postoperative clinical outcomes in HBV-related HCC patients. Thus, variants in and are associated with NM23 expression and clinical outcomes of HBV-related HCC patients, which may be regarded as potential biomarkers for this disease.

摘要

NM23的表达与肝细胞癌(HCC)复发密切相关,但影响NM23水平的遗传因素尚不清楚。利用公共数据库,研究了其在HCC中的诊断价值。共纳入424例乙型肝炎病毒(HBV)相关的HCC患者,进行全基因组关联研究,以鉴定与NM23表达水平相关的候选变异。此外,在后续分析中进行了逻辑回归模型、单倍型和生存分析。我们发现高NM23表达水平在HCC组织中具有诊断准确性,且在HBV相关的HCC患者中无复发生存期较差。银屑病易感性1候选基因1(PSORS1C1)和含StAR相关脂质跨膜结构域3(STARD3)附近的变异与NM23表达相关。PSORS1C1单倍型TGCACA和STAR D3单倍型GG对NM23表达具有良好的累积效应。此外,PSORS1C1中的变异仅与HCC患者的总生存期(rs556285588、rs3095301和rs3131003)相关,或与总生存期和无复发生存期(rs560052000和rs541820233)均相关。我们的研究结果表明,PSORS1C1和STAR D3位点的变异在NM23调控中起重要作用。此外,PSORS1C1中的变异是预测HBV相关HCC患者术后临床结局的潜在生物标志物。因此,PSORS1C1和STAR D3中的变异与HBV相关HCC患者的NM23表达和临床结局相关,可被视为该疾病的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4548/6312618/1be5e9ac2291/JO2018-6594169.001.jpg

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