«上一篇/Previous Article|本期目录/Table of Contents|下一篇/Next Article»

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

26卷

期数:

2020年06期

页码:

514-517

栏目:

基础医学

出版日期:

2020-11-20

文章信息/Info

Title:

Gene expression profiling reveals important characteristic genes in hepatocellular carcinoma

作者:

张萃萃¹; 2; 邓为民¹

1.天津医科大学基础医学院免疫学系，天津300070；2.天津市血液中心发血科，天津300110

Author(s):

ZHANG Cui-cui¹; 2;  DENG Wei-min¹

1. Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; 2.Department of Blood Distribution, Tianjin Blood Center, Tianjin 300110, China

关键词:

肝细胞癌; PPI方法; ELISA; SLC7A11; CCDC14

Keywords:

hepatocellular carcinoma;  PPI method;  ELISA;  SLC7A11;  CCDC14

分类号:

R730.3

DOI:

-

文献标志码:

A

摘要:

目的：生物信息学方法建立全面的肝细胞癌（HCC）差异表达基因谱以及初步筛选基于该恶性肿瘤样本的特征 基因。方法：利用R语言中的edgeR包分析不同组之间差异表达的基因（DEGs）。利用STRING数据库分析预测蛋白质的 功能联系和蛋白质相互作用。R语言的clusterProfiler包做GO（gene ontology）（包括biological process、 molecular function和cellular component）及KEGG（kyoto encyclopedia of genes and genomes）通路富集分析。 筛选差异基因显著富集的GO和KEGG分子途径。利用SLC7A11（solute carrier family 7 member 11）和CCDC14 （coiled-coil domain-containing 14）基因作为肝细胞癌的标志物，利用ELISA法进行检测（确诊的HCC阳性患者为 HCC组，共195例；HCC阴性正常人群为对照组，共107名），计算阳性率。结果：与癌旁对照样本相比，一共鉴定出454 个差异表达基因，其中高表达基因234个，低表达基因220个。PPI方法进一步筛选出排名前10的重要潜在基因，其中 SLC7A11和CCDC14两个基因排名靠前。利用富集分析，差异基因主要集中在neuroactive ligand-receptor interaction通路中。与对照组相比，HCC组SLC7A11和CCDC14存在显著的高表达[SLC7A11：（70.12±14.3） ng/mL比 （23.12±7.11）ng/mL，t=6.17，P<0.001；CCDC14：（6.17±2.31）pg/mL比（2.13±0.84）pg/mL，t=5.35， P<0.001]。SLC7A11针对HCC检测阳性率达到80.2%，而CCDC14达到68.8%。结论：SLC7A11和CCDC14可以作为HCC的两个 潜在的有效临床生物标志物。

Abstract:

Objective: To establish a comprehensive differentially expressed gene profile of hepatocellular carcinoma（HCC） by bioinformatics method and to screen the potential characteristic genes based on the malignant tumor samples. Methods: The edge package of R language was performed to analyze the differentially expressed genes（DEGs） among different groups. The STRING database was generated for better predicting functional relationship of protein and protein-protein interaction. Meanwhile, the cluster profiler functional package of R language was processed to generate GO（gene ontology） （including biological process, molecular function and cellular component） and KEGG（kyoto encyclopedia of genes and genomes） enrichment assay. GO and KEGG molecular pathways with significant enrichment of differentially expressed genes were screened. In addition, SLC7A11（solute carrier family 7 member 11） and CCDC14（coiled-coil domain-containing 14） genes were developed as specific biomarkers for HCC. ELISA method was utilized to analyze selected gene expression inexternal clinical experiments （HCC positive patients with 195 cases were HCC group, as well as HCC negative normal people with 107 cases were control group）, and positive rate was calculated. Results: Compared with the control samples, 454 differentially expressed genes were identified, including 234 upregulated genes and 220 downregulated genes. PPI method further screened out the top 10 primary potential genes, of which SLC7A11 and CCDC14 ranked the top. Using the enrichment analysis, the differentially expressed genes were mainly concentrated in neuroactive ligand-receptor interaction pathway.The concentrations of SLC7A11 and CCDC14 were significantly higher in HCC positive patients group[SLC7A11:（70.12±14.3） ng/mL vs. （23.12±7.11） ng/mL，t = 6.17, P< 0.001; CCDC14: （6.17±2.31） pg/mL vs.（2.13±0.84） pg/mL, t= 5.35, P< 0.001]. The positive rate of SLC7A11 was 80.2% and of CCDC14 was 68.8% for HCC respectively. Conclusion: SLC7A11 and CCDC14 can be used as two potential effective clinical biomarkers for HCC detection.

参考文献/References:

[1] El-Serag H B. Hepatocellular carcinoma[J]. N Engl J Med，2011， 365（1）:1118
[2] Lurje I，Czigany Z，Bednarsch J，et al. Treatment strategies for hepatocellular carcinoma a multidisciplinary approach[J]. Int J Mol Sci，2019，20（1）:1
[3] Colquhoun S D. Hepatocellular carcinoma[J]. Crit Rev Oncog，2016， 21（1）:93
[4] Forner A，Reig M，Bruix J. Hepatocellular carcinoma[J]. Lancet，2018，391（1）:1301
[5] Li S，Yang F，Ren X. Immunotherapy for hepatocellular carcinoma[J].Drug Discov Ther，2015，9（1） :363
[6] Villanueva A.Hepatocellular Carcinoma[J].N Engl J Med，2019, 38（1）:1450
[7] Golabi P，Rhea L，Henry L，et al. Hepatocellular carcinoma and non-alcoholic fatty liver disease [J]. Hepatol Int，2019，13（688）:94
[8] Kudo M. Targeted and immune therapies for hepatocellular carcinoma:predictions for 2019 and beyond[J].World J Gastroenterol，2019，25（789）:807
[9] Schlachterman A，Craft W W，Hilgenfeldt E，et al. Current and future treatments for hepatocellular carcinoma[J]. World J Gastroenterol，2015，21（84）:78
[10] Greten T F，Lai C W，Li G，et al. Targeted and immune-based therapies for hepatocellular carcinoma[J].Gastroenterol，2019，156（1）:510
[11] Grandhi M S，Kim A K，Ronnekleiv-Kelly S M，et al.Hepatocellular carcinoma: from diagnosis to treatment[J]. Surg Oncol，2016，25（1）:74
[12] 杨贵敏，赵运胜，王春华，等.肝细胞癌肿瘤标志物的研究进展[J].临床肝胆病杂志，2018，34（1）:199
[13] Wang L，Huang J，Jiang M，et al. AFP computational secreted network construction and analysis between human hepatocellular carcinoma （HCC） and no-tumor hepatitis/cirrhotic liver tissues[J].Tumor Biol，2010，31（1）:417
[14] Liu Z，Gartenhaus R B，Tan M，et al. Gene and pathway identification with Lp penalized Bayesian logistic regression[J]. BMC Bioinformatics，2008，9（1）:412
[15] Zhao Y，Xue F，Sun J，et al. Genome-wide methylation profiling of the different stages of hepatitis B virus-related hepatocellular carcinoma development in plasma cell-free DNA reveals potential biomarkers for early detection and high-risk monitoring of hepatocellular carcinoma[J]. Clin Epigenetics，2014，6（1）:30
[16] Yue C，Ren Y，Ge H，et al. Comprehensive analysis of potential prognostic genes for the construction of a competing endogenous RNA regulatory network in hepatocellular carcinoma[J]. OncoTargets Ther，2019，12（1）:561
[17] 许建辉，殷德涛. CCDC与恶性肿瘤的研究进展[J]. 国际外科学杂志，2014，41（9）:1

相似文献/References:

[1]周冷潇,韩 涛.慢性乙型病毒性肝炎肝硬化发生肝细胞癌的危险因素分析[J].天津医科大学学报,2017,23(03):214.
　ZHOU Leng-xiao,HAN Tao.Risk factors of hepatocellular carcinoma in patients with hepatitis B virus-related liver cirrhosis[J].Journal of Tianjin Medical University,2017,23(06):214.
[2]周冷潇,韩 涛,刘 芳.无创肝纤维化指标结合甲胎蛋白对乙型肝炎相关肝细胞癌的评估[J].天津医科大学学报,2017,23(05):415.
　ZHOU Leng-xiao,HAN Tao,LIU Fang.Assessment of non-invasive fibrosis indexes with alpha-fetoprotein?for? hepatitis B virus-related hepatocellular carcinoma[J].Journal of Tianjin Medical University,2017,23(06):415.
[3]张自立,石文霞,李 霖,等.肝癌血清中miRNA-183的表达及临床意义[J].天津医科大学学报,2017,23(06):519.
　ZHANG Zi-li,?SHI Wen-xia,LI Lin,et al.Expression and significance of serum microRNA-183 in hepatocellular carcinoma[J].Journal of Tianjin Medical University,2017,23(06):519.
[4]侯振宇,孔银龙,孙 林,等.92例晚期肝细胞癌患者肝切除预后及危险因素分析[J].天津医科大学学报,2018,24(05):425.
　HOU Zhen-yu,KONG Yin-long,SUN Lin,et al.Prognosis and survival risk factors for 92 advanced hepatocellular carcinoma patients after hepatectomy[J].Journal of Tianjin Medical University,2018,24(06):425.
[5]胡 源,许戈良,荚卫东,等.C1QL1蛋白在原发性肝细胞癌中的表达及其临床意义[J].天津医科大学学报,2019,25(04):329.
　HU Yuan,XU Ge-liang,JIA Wei-dong,et al.Expressions of C1QL1 protein inprimaryhepatocellular carcinoma and its clinical significance[J].Journal of Tianjin Medical University,2019,25(06):329.
[6]张杨,游阿彬,齐寒,等.负载化疗药物的外泌体对肝癌的靶向治疗研究[J].天津医科大学学报,2021,27(03):229.
　ZHANG Yang,YOU A-bin,QI Han,et al.Tumor-derived exosomes mediate targeted therapy in hepatocellular carcinoma mice[J].Journal of Tianjin Medical University,2021,27(06):229.
[7]王凤松,朱刘洋,白易,等.基于肿瘤突变负荷构建肝细胞癌风险评分预后模型[J].天津医科大学学报,2022,28(01):20.
　WANG Feng-song,ZHU Liu-yang,BAI Yi,et al.Identification of a risk score prognostic model of hepatocellular carcinoma based on tumor mutation burden[J].Journal of Tianjin Medical University,2022,28(06):20.
[8]赵耕,张盈莹,卓永,等.藏区慢性乙型肝炎患者使用PAGE-B模型对肝细胞癌的风险预测研究[J].天津医科大学学报,2022,28(06):654.
　ZHAO Geng,ZHANG Ying-ying,ZHUO Yong,et al.Risk prediction of hepatocellular carcinoma using the PAGE-B model in Tibetan patients with chronic hepatitis B[J].Journal of Tianjin Medical University,2022,28(06):654.
[9]张华,范松,刘冀琴,等.miR-129-5p通过靶向SALL4抑制肝癌细胞增殖、迁移和侵袭的实验研究[J].天津医科大学学报,2024,30(01):11.[doi:10.20135/j.issn.1006-8147.2024.01.0011]
　ZHANG Hua,FAN Song,LIU Jiqin,et al.The experimental study of miR-129-5p inhibiting proliferation， migration， and invasion of hepatocellular carcinoma by targeting to SALL4[J].Journal of Tianjin Medical University,2024,30(06):11.[doi:10.20135/j.issn.1006-8147.2024.01.0011]
[10]元喆悦,白易,童文,等.基于COVID-19相关基因的肝细胞癌分子分型及预后模型构建与验证[J].天津医科大学学报,2024,30(01):15.[doi:10.20135/j.issn.1006-8147.2024.01.0015]
　YUAN Zheyue,BAI Yi,TONG Wen,et al.Molecular typing of hepatocellular carcinoma based on COVID-19 related genes and construction and validation of prognostic model[J].Journal of Tianjin Medical University,2024,30(06):15.[doi:10.20135/j.issn.1006-8147.2024.01.0015]

备注/Memo

备注/Memo:

文章编号 1006-8147（2020）06-0514-04
基金项目 天津市自然科学基金重点项目（18YFZCSY00040 ）
作者简介 张萃萃（1986-）,女，主管技师，硕士在读，研究方向：肿瘤免疫; 通信作者：邓为民，E-mail： dengweimin@tmu.edu.cn。

常用功能

更新日期/Last Update: 2020-11-20