基于TCGA数据库分析CCDC34基因在肝细胞癌中的表达及意义

向晓辉; 毛骏; 李海

doi:10.3969/j.issn.1001-5256.2020.05.020

基于TCGA数据库分析CCDC34基因在肝细胞癌中的表达及意义

DOI: 10.3969/j.issn.1001-5256.2020.05.020

1. 天津市西青医院消化内科
2. 天津市肝脏胰腺纤维化与分子诊疗重点实验室
3. 武警后勤学院

基金项目:

天津市自然科学基金项目（17JCYBJC26700）；

详细信息

中图分类号: R735.7;TP311.13
计量
- 文章访问数: 1157
- HTML全文浏览量: 58
- PDF下载量: 160
- 被引次数: 0
出版历程
- 出版日期: 2020-05-20

Expression and clinical significance of CCDC34 in hepatocellular carcinoma:An analysis based on The Cancer Genome Atlas database

Department of Gastroenterology, Tianjin Xiqing Hospital, Tianjin 300380, China

Research funding:

摘要

摘要:
目的研究卷曲螺旋结构域蛋白34（CCDC34）基因在肝细胞癌中的表达以及临床价值,预测CCDC34基因在肝细胞癌发生发展中的作用。方法从癌症基因组图谱（TCGA）下载肝细胞癌数据集,获得CCDC34基因表达谱和临床信息。利用生物信息学方法,分析CCDC34基因在肝细胞癌中的表达水平与临床病理指标的相关性以及对预后的影响。用基因集富集分析（GSEA）预测CCDC34基因在肝细胞癌中调控的可能通路。计量资料2组间比较分别采用独立样本t检验及配对t检验。生存分析采用Kaplan-Meier法及log-rank检验;并运用Cox比例风险回归模型分析影响患者预后的危险因素。GSEA判断显著性富集的标准为P<0. 01,且错误发现率（FDR）<0. 05。结果在TCGA数据库中,CCDC34基因在肿瘤组织中高表达,其表达水平在TNM分期和肿瘤分级之间差异均有统计学意义（t值分别为2.118、3.622,P值分别为0. 035、<0. 001）。CCDC34基因高表达的患者总生存期明显低于CCDC34基因低表达的患者（χ2=21.716,P<0. 05）...
- 癌,肝细胞 /
- 卷曲螺旋结构域蛋白34 /
- 基因表达 /
- 计算生物学
Abstract:
Objective To investigate the expression and clinical value of coiled-coil domain-containing protein 34(CCDC34) in hepatocellular carcinoma(HCC), and to predict the role of CCDC34 in the development and progression of HCC.Methods The datasets of HCC were downloaded from The Cancer Genome Atlas(TCGA) to obtain the expression profile and clinical information of the CCDC34 gene. The bioinformatics method was used to analyze the expression of CCDC34 in HCC, its correlation with clinicopathological parameters, and its influence on prognosis. The gene set enrichment analysis(GSEA) was used to predict the possible pathways regulated by the CCDC34 gene in HCC. The independent samplest-test and the pairedt-test were used for comparison of continuous data between two groups; the Kaplan-Meier method and the log-rank test were used for survival analysis; the Cox proportional-hazards regression model analysis was used to investigate the influencing factors for prognosis.P< 0. 01 was the standard for judging significant enrichment in GSEA, and the false discovery rate was <0.05.Results In TCGA database, CCDC34 was highly expressed in tumor tissue, and there was a significant difference in the expression of CCDC34 between patients with different TNM stages and tumor grades(t =2. 118 and 3. 622,P= 0. 035 andP< 0. 001). The patients with high expression of CCDC34 had a significantly shorter overall survival time than those with low expression （χ2 =21.716,P<05). The multivariate Cox regression analysis showed that the expression of CCDC34(HR =2. 287,95%CI:1. 312-3. 987)and TNM stage(HR =1.943,95%CI:1.101-3.429) were independent risk factors for the overall survival time of patients with HCC(allP< 0. 05).The enrichment of 8 pathway gene sets, including base excision repair and spliceosome, was observed in the samples with high expression of CCDC34(P< 0. 01, FDR < 0. 05).Conclusion CCDC34 may play a vital role in the development and progression of HCC and thus become a new prognostic indicator and a potential therapeutic target.
- carcinoma,hepatocellular /
- coiled-coil domain-containing protein /
- gene expression /
- computational biology

HTML全文

参考文献(26)

[1] GOLABI P, FAZEL S, OTGONSUREN M, et al. Mortality assessment of patients with hepatocellular carcinoma according to underlying disease and treatment modalities[J]. Medicine(Baltimore), 2017, 96(9):e5904.

[2] MEDAVARAM S, ZHANG Y. Emerging therapies in advanced hepatocel ular carcinoma[J]. Exp Hematol Oncol, 2018, 7:17.

[3] FERLAY J, COLOMBET M, SOERJOMATARAM I, et al. Estimating the global cancer incidence and mortality in 2018:GLOBOCAN sources and methods[J]. Int J Cancer, 2019,144(8):1941-1953.

[4] BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424.

[5] GHOURI YA, MIAN I, ROWE JH. Review of hepatocel ular carcinoma:Epidemiology, etiology, and carcinogenesis[J]. J Carcinog, 2017, 16:1.

[6] LUPAS AN, GRUBER M. The structure of alpha-helical coiled coils[J]. Adv Protein Chem, 2005, 70:37-78.

[7] YIN DT, XU J, LEI M, et al. Characterization of the novel tumor-suppressor gene CCDC67 in papillary thyroid carcinoma[J]. Oncotarget, 2016, 7(5):5830-5841.

[8] JIANG GY, ZHANG XP, ZHANG Y, et al. Coiled-coil domaincontaining protein 8 inhibits the invasiveness and migration of nonsmal cel lung cancer cells[J]. Hum Pathol, 2016, 56:64-73.

[9] TANOUCHI A, TANIUCHI K, FURIHATA M, et al. CCDC88A,a prognostic factor for human pancreatic cancers, promotes the motility and invasiveness of pancreatic cancer cells[J]. J Exp Clin Cancer Res, 2016, 35(1):190.

[10] HSIAO KY, LIN YC, GUPTA SK, et al. Noncoding effects of circular RNA CCDC66 promote colon cancer growth and metastasis[J]. Cancer Res, 2017, 77(9):2339-2350.

[11] KUTSCHE K, GLAUNER E, KNAUF S, et al. Cloning and characterization of the breakpoint regions of a chromosome 11;18 translocation in a patient with hamartoma of the retinal pigment epithelium[J]. Cytogenet Cel Genet, 2000, 91(1-4):141-147.

[12] ROBINSON MD, MCCARTHY DJ, SMYTH GK. edgeR:A Bioconductor package for differential expression analysis of digital gene expression data[J]. Bioinformatics, 2010, 26(1):139-140.

[13] DILLIES MA, RAU A, AUBERT J, et al. A comprehensive evaluation of normalization methods for Illumina high-throughput RNA sequencing data analysis[J]. Brief Bioinform, 2013,14(6):671-683.

[14] SUBRAMANIAN A, TAMAYO P, MOOTHA VK, et al. Gene set enrichment analysis:A knowledge-based approach for interpreting genome-wide expression profiles[J]. Proc Natl Acad Sci U S A, 2005, 102(43):15545-15550.

[15] KANEHISA M, FURUMICHI M, TANABE M, et al. KEGG:New perspectives on genomes, pathways, diseases and drugs[J].Nucleic Acids Res, 2017, 45(D1):d353-d361.

[16] SUBRAMANIAN A, KUEHN H, GOULD J, et al. GSEA-P:A desktop application for Gene Set Enrichment Analysis[J].Bioinformatics, 2007, 23(23):3251-3253.

[17] MAEYAMA Y, OTSU M, KUBO S, et al. Intracellular estrogen receptor-binding fragment-associated antigen 9 exerts in vivo tumor-promoting effects via its coiled-coil region[J]. Int J Oncol, 2011, 39(1):41-49.

[18] LIU Z, MAI C, YANG H, et al. Candidate tumour suppressor CCDC19 regulates miR-184 direct targeting of C-Myc thereby suppressing cell growth in non-small cell lung cancers[J]. J Cell Mol Med, 2014, 18(8):1667-1679.

[19] GENG W, LIANG W, FAN Y, et al. Overexpression of CCDC34 in colorectal cancer and its involvement in tumor growth, apoptosis and invasion[J]. Mol Med Rep, 2018, 17(1):465-473.

[20] HU DD, LI PC, HE YF, et al. Overexpression of coiled-coil domain-containing protein 34(CCDC34)and its correlation with angiogenesis in esophageal squamous cell carcinoma[J]. Med Sci Monit, 2018, 24:698-705.

[21] STARK GR, TAYLOR WR. Control of the G2/M transition[J].Mol Biotechnol, 2006, 32(3):227-248.

[22] GONG Y, QIU W, NING X, et al. CCDC34 is up-regulated in bladder cancer and regulates bladder cancer cell proliferation,apoptosis and migration[J]. Oncotarget, 2015, 6(28):25856-25867.

[23] PANI B, NUDLER E. Mechanistic insights into transcription coupled DNA repair[J]. DNA Repair(Amst), 2017, 56:42-50.

[24] MAHAMUD O, SO J, CHUA M, et al. Targeting DNA repair for precision radiotherapy:Balancing the therapeutic ratio[J].Curr Probl Cancer, 2017, 41(4):265-272.

[25] MURAI J. Targeting DNA repair and replication stress in the treatment of ovarian cancer[J]. Int J Clin Oncol, 2017, 22(4):619-628.

[26] GENTIEN D, KOSMIDER O, NGUYEN-KHAC F, et al. A common alternative splicing signature is associated with SF3B1 mutations in malignancies from different cell lineages[J]. Leukemia, 2014, 28(6):1355-1357.

施引文献

资源附件(0)

访问统计