Association between the expression of centromere protein F and prognosis in patients with hepatocellular carcinoma:An analysis using GEO database
-
摘要: 目的探讨着丝粒蛋白F(CENPF)基因在肝细胞癌(HCC)患者组织中的表达情况及与临床特征和预后的相关性。方法利用在线工具Oncomine分析CENPF在HCC与正常肝组织的表达情况,从美国国立生物技术信息中心的GEO数据库下载相关芯片数据(GSE14520),收集215例HCC组织的基因表达谱及相关临床数据,将其分为CENPF低表达组(n=107)和CENPF高表达组(n=108)。对样本中的CENPF基因表达数据及其对应的临床信息进行分析。计量资料组间比较采用t检验;计数资料组间比较采用χ2检验;生存分析采用log-rank(Mantel-Cox)检验;生存资料单因素及多因素分析采用Cox比例风险模型。结果数据集证实HCC组织中CENPF表达水平明显高于正常肝组织(t=12.217,P<0.001)。CENPF基因表达水平与AFP水平、肿瘤大小、TNM分期、转移风险有关系(χ2值分别为6.463、4.338、7.951、17.331,P值均<0.05)。生存分析显示CENPF高表达患者预后明显差于CENPF低表达组(风险比=1...Abstract: Objective To investigate the association of the expression of centromere protein F ( CENPF) with clinical features and prognosis in patients with hepatocellular carcinoma ( HCC) . Methods The online tool Oncomine was used to measure the expression of CENPF in HCC tissue and normal liver tissue. Related chip data ( GSE14520) were downloaded from the GEO database of National Center for Biotechnology Information. The gene expression profile and related clinical data of 215 HCC tissue samples were collected, and these samples were divided into low CENPF expression group with 107 samples and high CENPF expression group with 108 samples. The expression of CENPF and related clinical information were analyzed. The t-test was used for comparison of continuous data between groups; the chi-square test was used for comparison of categorical data between groups; the log-rank ( Mantel-Cox) test was used for survival analysis; the Cox proportional hazards model was used for univariate and multivariate analyses of survival data. Results The datasets demonstrated that HCC tissue samples had a significantly higher expression level of CENPF than normal liver tissue samples ( t = 12. 217, P < 0. 001) . The expression level of CENPF was associated with alpha-fetoprotein ( AFP) level, tumor size, TNM stage, and metastasis risk ( χ2= 6. 463, 4. 338, 7. 951, and 17. 331, all P < 0. 05) . The survival analysis showed that the patients with high CENPF expression had a significantly poorer prognosis than those with low CENPF expression ( hazard ratio = 1. 92, 95% confidence interval: 1. 24-2. 96, P = 0. 005) . The univariate Cox analysis showed that the prognosis of HCC patients was associated with AFP level, tumor diameter, liver cirrhosis, tumor stage, metastasis risk, and CENPF expression ( all P < 0. 05) ; the multivariate Cox analysis showed that liver cirrhosis, tumor stage, and high CENPF expression were independent risk factors for the prognosis of HCC patients ( all P < 0. 05) . Conclusion High CENPF expression is associated with the progression of HCC, and CENPF might be used as a potential prognostic biomarker for HCC patients.
-
Key words:
- carcinoma, hepatocellular /
- centromere protein F /
- gene expression /
- prognosis
-
[1]PASCUAL S, HERRERA I, IRURZUN J.New advances in hepatocellular carcinoma[J].World J Hepatol, 2016, 8 (9) :421-438. [2]KIM JU, SHARIFF MI, CROSSEY MM, et al.Hepatocellular carcinoma:Review of disease and tumor biomarkers[J].World J Hepatol, 2016, 8 (10) :471-484. [3]LLOVET JM, BRU'C, BRUIX J.Prognosis of hepatocellular carcinoma:The BCLC staging classification[J].Semin Liver Dis, 1999, 19 (3) :329-338. [4]WEDD JP, NORDSTROM E, NYDAM T, et al.Hepatocellular carcinoma in patients listed for liver transplantation:Current and future allocation policy and management strategies for the individual patient[J].Liver Transpl, 2015, 21 (12) :1543-1552. [5]MAO YQ, LIANG XM, FU HY, et al.Effects ofβ-elemene onα-tubulin of Human Hepatocarcinoma Hep G-2 Cells[J].China Cancer, 2012, 21 (2) :145-149. (in Chinese) 毛雨秋, 梁鑫淼, 付海雁, 等.β-揽香烯注射液对人肝癌Hep G-2细胞微观蛋白α的影响[J].中国肿瘤, 2012, 21 (2) :145-149. [6]LU LG.Advances in early screening and diagnosis of hepatocellular carcinoma[J].J Clin Hepatol, 2017, 33 (7) :1257-1261. (in Chinese) 陆伦根.原发性肝癌的早期筛查及诊断[J].临床肝胆病杂志, 2017, 33 (7) :1257-1261. [7]VARIS A, SALMELA AL, KALLIO MJ.Cenp-F (mitosin) is more than a mitotic marker[J].Chromosoma, 2006, 115 (4) :288-295. [8]BRENDLE A, BRANDT A, JOHANSSON R, et al.Single nucleotide polymorphisms in chromosomal instability genes and risk and clinical outcome of breast cancer:A Swedish prospective case-control study[J].Eur J Cancer, 2009, 45 (3) :435-442. [9]CHEN WB, CHENG XB, DING W, et al.Centromere protein F and survivin are associated with high risk and a poor prognosis in colorectal gastrointestinal stromal tumours[J].J Clin Pathol, 2011, 64 (9) :751-755. [10]CAO JY, LIU L, CHEN SP, et al.Prognostic significance and therapeutic implications of centromere protein F expression in human nasopharyngeal carcinoma[J].Mol Cancer, 2010, 9:237. [11]ROESSLER S, JIA HL, BUDHU A, et al.A unique metastasis gene signature enables prediction of tumor relapse in early-stage hepatocellular carcinoma patients[J].Cancer Res, 2010, 70 (24) :10202-10212. [12]PFALTZGRAFF ER, ROTH GM, MILLER PM, et al.Loss of CENP-F results in distinct microtubule-related defects without chromosomal abnormalities[J].Mol Biol Cell, 2016, 27 (13) :1990-1999. [13]FRITZLER MJ, RATTNER JB, LUFT LM, et al.Historical perspectives on the discovery and elucidation of autoantibodies to centromere proteins (CENP) and the emerging importance of antibodies to CENPF[J].Autoimmun Rev, 2011, 10 (4) :194-200. [14]LIU SQ, CHEN W, YANG LH.Effect of down-regulation of CENP-F by RNAi on proliferation in human glioma cell line U251[J].Lingnan J Emerg Med, 2015, 20 (5) :391-393. (in Chinese) 刘淑琼, 陈伟, 杨炼红.RNA干扰下调CENP-F对U251细胞增殖的影响[J].岭南急诊医学杂志, 2015, 20 (5) :391-393. [15]ZHOU HB, HU HP.Challenges in precise treatment for primary liver cancer based on gene mutation[J].J Clin Hepatol, 2017, 33 (7) :1209-1210. (in Chinese) 周华邦, 胡和平.基于基因突变的原发性肝癌精准治疗的挑战[J].临床肝胆病杂志, 2017, 33 (7) :1209-1210. [16]LIN SC, KAO CY, LEE HJ, et al.Dysregulation of miRNAsCOUP-TFII-FOXM1-CENPF axis contributes to the metastasis of prostate cancer[J].Nat Commun, 2016, 7:11418. [17]HOLT SV, VERGNOLLE MA, HUSSEIN D, et al.Silencing Cenp-F weakens centromeric cohesion, prevents chromosome alignment and activates the spindle checkpoint[J].J Cell Sci, 2005, 118 (Pt20) :4889-4900. [18]KIM HE, KIM DG, LEE KJ, et al.Frequent amplification of CENPF, GMNN and CDK13 genes in hepatocellular carcinomas[J].PLo S One, 2012, 7 (8) :e43223. [19]ZHUO YJ, XI M, WAN YP, et al.Enhanced expression of centromere protein F predicts clinical progression and prognosis in patients with prostate cancer[J].Int J Mol Med, 2015, 35 (4) :966-972. [20]BROWN HK, OTTEWELL PD, COLEMAN RE, et al.The kinetochore protein Cenp-F is a potential novel target for zoledronic acid in breast cancer cells[J].J Cell Mol Med, 2011, 15 (3) :501-513. [21]MI YJ, GAO J, XIE JD, et al.Prognostic relevance and therapeutic implications of centromere protein F expression in patients with esophageal squamous cell carcinoma[J].Dis Esophagus, 2013, 26 (6) :636-643. [22]ZHU XL, MANCINI MA, CHANG KH, et al.Characterization of a novel 350-kilodalton nuclear phosphoprotein that is specifically involved in mitotic-phase progression[J].Mol Cell Biol, 1995, 15 (9) :5017-5029.
本文二维码
计量
- 文章访问数: 3059
- HTML全文浏览量: 13
- PDF下载量: 469
- 被引次数: 0