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  • 汪慧,胡亮,邹珊珊,刘文迪,周华邦,胡和平.C型凝集素结构域家族1成员B在肝细胞癌中的表达及临床意义[J].第二军医大学学报,2019,40(5):547-553    [点击复制]
  • WANG Hui,HU Liang,ZOU Shan-shan,LIU Wen-di,ZHOU Hua-bang,HU He-ping.Expression of C-type lectin domain family 1 member B in hepatocellular carcinoma and its clinical signifcance[J].Acad J Sec Mil Med Univ,2019,40(5):547-553   [点击复制]
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C型凝集素结构域家族1成员B在肝细胞癌中的表达及临床意义
汪慧1,胡亮2,邹珊珊1,刘文迪1,周华邦1,胡和平1*
0
(1. 海军军医大学(第二军医大学)东方肝胆外科医院肝胆内一科, 上海 200438;
2. 上海药物转化工程技术研究中心, 上海 201203
*通信作者)
摘要:
目的 探讨C型凝集素结构域家族1成员B(CLEC1B)在肝细胞癌(HCC)组织中的表达及其与HCC患者临床病理特征和预后的关系。方法 利用基因表达汇编(GEO)数据库检索HCC组织芯片数据(GSE49515、GSE115018)对癌组织及正常对照样本中的基因进行差异表达分析。在肿瘤基因组图谱(TCGA)数据库筛选HCC转录组数据集,分析CLEC1B在HCC中的差异表达。采用基因集富集分析(GSEA)探寻HCC中与CLEC1B相关的信号通路。收集37例HCC患者的癌组织和相应的癌旁组织,采用实时荧光定量PCR法检测CLEC1B mRNA表达,蛋白质印迹分析法检测CLEC1B蛋白表达,并采用χ2检验分析CLEC1B表达与患者临床病理特征的关系,通过Kaplan-Meier法和log-rank检验分析CLEC1B mRNA表达与HCC患者预后的关系;留取37例HCC患者和37名健康志愿者血液标本,用酶联免疫吸附试验检测血浆中CLEC1B水平,通过受试者工作特征(ROC)曲线评估CLEC1B对HCC的诊断价值。结果 CLEC1B在HCC癌组织中低表达,CLEC1B的低表达与HCC患者的肿瘤出血有关(P<0.01)。血浆中CLEC1B水平可作为诊断HCC的生物标志物,以62.44 ng/mL作为截断值时,CLEC1B的诊断效能最佳(ROC曲线下面积为0.966,灵敏度为92.7%,特异度为91.3%)。高表达CLEC1B的HCC患者总生存期长于低表达CLEC1B的患者,差异有统计学意义(P<0.01)。在HCC中,CLEC1B基因与ATR通路(ATM and Rad3-related pathway)、细胞周期通路、DNA修复通路、myc信号通路呈现出一致的表达差异趋势。结论 CLEC1B在HCC中低表达并与肿瘤出血有关,CLEC1B低表达的患者预后较差。
关键词:  C型凝集素结构域家族1成员B  肝细胞癌  诊断  预后  基因富集
DOI:10.16781/j.0258-879x.2019.05.0547
投稿时间:2019-04-10修订日期:2019-05-15
基金项目:国家自然科学基金青年科学基金(81502093).
Expression of C-type lectin domain family 1 member B in hepatocellular carcinoma and its clinical signifcance
WANG Hui1,HU Liang2,ZOU Shan-shan1,LIU Wen-di1,ZHOU Hua-bang1,HU He-ping1*
(1. Department of Hepatobiliary Disease(Ⅰ), Eastern Hepatobiliary Surgery Hospital, Naval Medical University(Second Military Medical University), Shanghai 200438, China;
2. Shanghai Engineering Research Center of Pharmaceutical Translation & Shanghai Industrial Technology Institute, Shanghai 201203, China
*Corresponding author)
Abstract:
Objective To explore the expression of C-type lectin domain 1 member B (CLEC1B) in hepatocellular carcinoma (HCC) tissues and its relationship with the clinicopathological characteristics and prognosis of HCC patients. Methods HCC tissue microarray data (GSE49515, GSE115018) were retrieved from Gene Expression Omnibus (GEO) database to analyze the differential expression of genes between cancer tissues and normal control tissues. HCC transcriptome datasets were screened from The Cancer Genome Atlas (TCGA) database to analyze the differential expression of CLEC1B in HCC tissues. Gene Set Enrichment Analysis (GSEA) was used to search for the signaling pathways related to CLEC1B in HCC. The cancer tissues and corresponding paracancerous tissues were collected from 37 HCC patients. The expression of CLEC1B mRNA was detected by quantitative real-time PCR, the expression of CLEC1B protein was detected by Western blotting. χ2 test was performed to analyze the relationship between CLEC1B expression and clinicopathological characteristics of HCC patients. Kaplan-Meier method and log-rank test were performed to analyze the relationship between CLEC1B mRNA expression and prognosis of HCC patients. The blood samples were collected from 37 HCC patients and 37 healthy volunteers. The concentration of CLEC1B in plasma was measured by enzyme-linked immunosorbent assay. The diagnostic value of CLEC1B for HCC was evaluated by receiver operating characteristic (ROC) curve. Results The expression of CLEC1B was low in HCC cancer tissues, and the low expression of CLEC1B in HCC tissues was associated with tumor hemorrhage (P<0.01). The concentration of CLEC1B in plasma could be used as a biomarker for the diagnosis of HCC. The best diagnostic efficiency of CLEC1B was obtained by using 62.44 ng/mL as cut-off value (the area under the ROC curve was 0.966, the sensitivity was 92.7%, and the specificity was 91.3%). The HCC patients with high CLEC1B expression had a longer overall survival than those with low CLEC1B expression, and the difference was significant (P<0.01). In HCC, CLEC1B gene showed a consistent trend of differential expression with ATM and Rad3-related pathway (ATR pathway), cell cycle pathway, DNA repair pathway and myc signaling pathway. Conclusion The low expression of CLEC1B in HCC is related to tumor hemorrhage, and the prognosis of HCC patients with low expression of CLEC1B is poor.
Key words:  C-type lectin domain family 1 member B  hepatocellular carcinoma  diagnosis  prognosis  gene enrichment