Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (6): 94-102.doi: 10.6040/j.issn.1671-7554.0.2021.0231

Previous Articles     Next Articles

Construction of circRNA-mediated ceRNA network and prognostic assessment model for bladder cancer

MI Qi, SHI Shuang, LI Juan, LI Peilong, DU Lutao, WANG Chuanxin   

  1. Department of Clinical Laboratory, The Second Hospital of Shandong University, Jinan 250033, Shandong, China
  • Published:2021-06-10

Abstract: Objective To identify the differentially expressed circular RNAs(circRNAs)and construct a circRNAs-mediated ceRNA network and a prognostic assessment model. Methods Data were downloaded from Gene Expression Omnibus(GEO)and The Cancer Genome Atlas(TCGA)database. Differential expressed analysis was performed to explore the differentially expressed RNAs in bladder cancer tissues with the standard of |log2 fold change(log2FC)|>1, P<0.05. Based on multiple detabases, such as TCGA and CircInteractome, the circRNA-miRNA-mRNA ceRNA network was constructed, and functional enrichment analysis of mRNAs was conducted. Subsequently, the relationship of mRNAs in ceRNA network was analyzed through the String database. The mRNAs related to prognosis were screened with univariate Cox regression model, and a prognostic assessment model was constructed. A ROC curve was drawn with “time ROC” package to evaluate the effectiveness of the model. Results Differential expressed analysis screened out 4 circRNAs, including hsa_circ_0102787, hsa_circ_0103114, hsa_circ_0102402 and hsa_circ_0104387. A ceRNA network was constructed, which contained 4 circRNAs, 23 miRNAs and 86 mRNAs. Functional enrichment analysis showed those mRNAs participated in several cancer-related pathways. The interaction between mRNAs in the ceRNA network was visualized by PPI network. Survival analysis revealed that 6 mRNAs were related to the prognosis of bladder cancer. Then, a prognostic assessment model was constructed based on “the risk score=(-0.356 9)×ABRACL+(-0.264 4)×MAP3K8.” Kaplan Meier analysis showed patients with high risks had a poor prognosis(P<0.001), and the AUC of the five-year overall survival rate was 0.744. Conclusion This study identififed 4 differentially expressed circRNAs, and constructed a circRNA-miRNA-mRNA network and a prognostic assessment model, which provides a new insight for the exploration of the occurrence and development of bladder cancer.

Key words: Bladder cancer, circRNAs, ceRNA, Prognosis, Cox regression model

CLC Number: 

  • R737.14
[1] Antoni S, Ferlay J, Soerjomataram I, et al. Bladder cancer incidence and mortality: a global overview and recent trends [J]. Eur Urol, 2017, 71(1): 96-108.
[2] 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.
[3] Robertson AG, Kim J, Al-Ahmadie H, et al. Comprehensive molecular characterization of muscle-invasive bladder cancer [J]. Cell, 2017, 171(3): 540-556.
[4] Kamat AM, Hahn NM, Efstathiou JA, et al. Bladder cancer [J]. Lancet, 2016, 388(10061): 2796-2810.
[5] Witjes JA, Lebret T, Comperat EM, et al. Updated 2016 EAU Guidelines on muscle-invasive and metastatic bladder cancer [J]. Eur Urol, 2017, 71(3): 462-475.
[6] Dreicer R. Chemotherapy for advanced urothelial cancer: end of the beginning? [J]. Lancet Oncol, 2017, 18(5): 567-569.
[7] Cambier S, Sylvester RJ, Collette L, et al. EORTC nomograms and risk groups for predicting recurrence, progression, and disease-specific and overall survival in non-muscle-invasive stage Ta-T1 urothelial bladder cancer patients treated with 1-3 years of maintenance bacillus calmette-guerin [J]. Eur Urol, 2016, 69(1): 60-69.
[8] Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs [J]. Nat Biotechnol, 2014, 32(5): 453-461.
[9] Liu YC, Li JR, Sun CH, et al. CircNet: a database of circular RNAs derived from transcriptome sequencing data [J]. Nucleic Acids Res, 2016, 44(D1): D209-215.
[10] Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency [J]. Nature, 2013, 495(7441): 333-338.
[11] Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition [J]. Nature, 2014, 505(7483): 344-352.
[12] Su Y, Feng W, Shi J, et al. Correction to: circRIP2 accelerates bladder cancer progression via miR-1305/Tgf-β2/smad3 pathway [J]. Mol Cancer, 2021, 20(1): 1. doi: 10.1186/s12943-019-1129-5.
[13] Su H, Tao T, Yang Z, et al. Circular RNA cTFRC acts as the sponge of MicroRNA-107 to promote bladder carcinoma progression [J]. Mol Cancer, 2019, 18(1): 27. doi: 10.1186/s12943-019-0951-0.
[14] Meng S, Zhou H, Feng Z, et al. CircRNA: functions and properties of a novel potential biomarker for cancer [J]. Mol Cancer, 2017, 16(1): 94. doi: 10.1186/s12943-017-0663-2.
[15] Wang Z, Jensen MA, Zenklusen JC. A practical guide to the cancer genome atlas(TCGA)[J]. Methods in molecular biology(Clifton, NJ), 2016, 1418: 111-141. doi: 10.1007/978-1-4939-3578-9_6.
[16] Ritchie ME, Phipson B, Wu D, et al. limma powers differential expression analyses for RNA-sequencing and microarray studies [J]. Nucleic acids research, 2015, 43(7): e47. doi: 10.1093/nar/gkv007.
[17] 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.
[18] Dudekula DB, Panda AC, Grammatikakis I, et al. CircInteractome: a web tool for exploring circular RNAs and their interacting proteins and microRNAs [J]. RNA Biol, 2016, 13(1): 34-42.
[19] Jiang J, Bi Y, Liu XP, et al. To construct a ceRNA regulatory network as prognostic biomarkers for bladder cancer [J]. J Cell Mol Med, 2020, 24(9): 5375-5386.
[20] Otasek D, Morris JH, Boucas J, et al. Cytoscape Automation: empowering workflow-based network analysis [J]. Genome Biol, 2019, 20(1): 185. doi: 10.1186/s13059-019-1758-4.
[21] 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.
[22] Gene OC. Gene ontology consortium: going forward [J]. Nucleic Acids Res, 2015, 43(Database issue): D1049-1056.
[23] Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets [J]. Nucleic Acids Res, 2019, 47(D1): D607-D613.
[24] Weng W, Wei Q, Toden S, et al. Circular RNA ciRS-7-A promising prognostic biomarker and a potential therapeutic target in colorectal cancer [J]. Clin Cancer Res, 2017, 23(14): 3918-3928.
[25] Cheng Z, Yu C, Cui S, et al. circTP63 functions as a ceRNA to promote lung squamous cell carcinoma progression by upregulating FOXM1 [J]. Nat Commun, 2019, 10(1): 3200. doi: 10.1038/s41467-019-11162-4.
[26] Zeng Z, Zhou W, Duan L, et al. Circular RNA circ-VANGL1 as a competing endogenous RNA contributes to bladder cancer progression by regulating miR-605-3p/VANGL1 pathway[J]. J Cell Physiol, 2019, 234(4): 3887-3896.
[27] 史爽, 李娟, 米琦, 等. 胃癌miRNAs预后风险评分模型的构建与应用[J]. 山东大学学报(医学版), 2020, 58(7): 47-52. SHI Shuang, LI Juan, MI Qi, et al. Construction and application of a miRNAs prognostic risk assessment model of gastric cancer [J]. Journal of Shandong University(Health Sciences), 2020, 58(7): 47-52.
[28] Chen Y, Xu T, Xie F, et al. Evaluating the biological functions of the prognostic genes identified by the Pathology Atlas in bladder cancer [J]. Oncol Rep, 2021, 45(1): 191-201.
[29] Vougioukalaki M, Kanellis DC, Gkouskou K, et al. Tpl2 kinase signal transduction in inflammation and cancer[J]. Cancer Letters, 2011, 304(2): 80-89.
[1] ZHENG Su, CHEN Shuhua, LI Hua, DENG Jie, CHEN Chunhong, WANG Xiaohui, FENG Weixing, HAN Xiaodi, ZHANG Yujia, LI Na, LI Mo, FANG Fang. Correlation between EEG variations and BASED evaluation of the efficacy of ACTH treatment in 54 cases of infantile spasms [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 91-96.
[2] WANG Lihui, GAO Min, KONG Beihua. Angiosarcoma of the uterus: a report of 2 cases and literature review [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 108-112.
[3] HE Shiqing, LI Wanwan, DONG Shuqing, MOU Jingyi, LIU Yuying, WEI Siyu, LIU Zhao, ZHANG Jiaxin. Construction of a prognostic risk model of pyroptosis-related genes in breast cancer based on database [J]. Journal of Shandong University (Health Sciences), 2022, 60(8): 34-43.
[4] ZHANG Yufeng, XU Min, XING Xiuli, PANG Shuguang, HU Keqing. Epidemiological characteristics of 689 patients with non-ST-segment elevation myocardial infarction [J]. Journal of Shandong University (Health Sciences), 2022, 60(7): 118-122.
[5] LI Linlin, WANG Kai. Prediction of hepatocellular carcinoma prognostic genes based on bioinformatics [J]. Journal of Shandong University (Health Sciences), 2022, 60(5): 50-58.
[6] SUN Zhenguo, TIAN Hui. Optimization of the procedures in minimally invasive esophagectomy: the Qilu practices [J]. Journal of Shandong University (Health Sciences), 2022, 60(11): 33-37.
[7] ZHU Yongcun, ZHAO Xiushi, SUN Nannan, YAO Zhigang, ZHOU Xingchen, MU Kun. Prostate clear cell adenocarcinomas: a report of 3 cases and literature review [J]. Journal of Shandong University (Health Sciences), 2022, 60(11): 102-107.
[8] SHI Xiaohan, LI Huayu, LI Feng. Prognostic factors of elderly patients with glioblastoma treated with Stupp treatment [J]. Journal of Shandong University (Health Sciences), 2022, 60(10): 42-48.
[9] CHEN Liyu, XIAO Juan, LYU Xianzhong, DUAN Baomin, HONG Fanzhen. Risk factors influencing prognosis of lower extremity deep vein thrombosis in pregnant and parturient women [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 38-42.
[10] TIAN Yaotian, WANG Bao, LI Yeqin, WANG Teng, TIAN Liwen, HAN Bo, WANG Cuiyan. Machine learning models based on interpretive CMR parameters can predict the prognosis of pediatric myocarditis [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 43-49.
[11] LI Wanwan, ZHOU Wenkai, DONG Shuqing, HE Shiqing, LIU Zhao, ZHANG Jiaxin, LIU Bin. Construct of a risk assessment model of breast cancer immune-related lncRNAs based on the database information [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 74-84.
[12] CHU Yan, LIU Duanrui, ZHU Wenshuai, FAN Rong, MA Xiaoli, WANG Yunshan, JIA Yanfei. Expressions of DNA methyltransferases in gastric cancer and their clinical significance [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 1-9.
[13] GAO Jinmei, ZHANG Xianglian, LIU Tieju. Correlation between plasma D-dimer and metastasis in 109 cases of bladder cancer [J]. Journal of Shandong University (Health Sciences), 2021, 59(3): 98-102.
[14] LI Xiangqing, YIN Xin, ZHAO Xuelian, ZHAO Peiqing. Expression and clinical significance of circulating CD56bright subset of NK cells in patients with Parkinsons disease [J]. Journal of Shandong University (Health Sciences), 2021, 59(2): 34-40.
[15] ZENG Rui, HU Xinting, YUN Xiaoya, TIAN Zheng, LI Qing, LIU Jie, ZHANG Ya, WANG Xin. Fluorescence in situ hybridization in the diagnosis of 197 cases of chronic lymphocytic leukemia [J]. Journal of Shandong University (Health Sciences), 2021, 59(11): 35-40.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] ZHANG Jie,LI Zhen-hua,SUN Jin-hao,BAO Li-hua,LIU Yue-peng. Protective effects of the invariable magnetic field on oxidative injured Schwann cells[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(3): 229 -232 .
[2] ZHENG Min,HAO Yue-wei,LIU Xue-ping,ZHAO Ting-ting. Relationship between the HPA-2 and Kozak sequence polymorphism of platelet membrane glycoprotein and cerebral infarction[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(3): 292 -295 .
[3] . [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(10): 995 .
[4] JIANG Hong-ju,LI Run-zhi, WANG Ying,XU Dong-mei,ZHANG Mei,ZHANG Yun,LI Ji-fu. Relationship between the plasma level of matrix metalloproteinase-9 and structural characteristics of plaques and percutaneous coronary intervention [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(10): 966 -970 .
[5] WANG Shu-qin,QI Feng,WU Jian-bo,SUN Bao-zhu. Effect of calcium in ropivacaine-induced smooth muscle contraction of the aorta in rats in vitro[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(8): 773 -776 .
[6] TENG Xue-ren,ZHAO Yong-sheng,HU Guang-liang,ZHOU Lun,LI Jian-min. Characteristics of microcosmic changes following tendon allograft transplantation preserved by two methods under light microscopy and transmission electron microscopy[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(10): 945 -950 .
[7] JIAO Fang-fang,LIU Shi-qing,LI Fei,LI Chang-sheng,WANG Qin,SUN Qing,LU Wei. Therapeutic effects of Huayulifei on expression of SMAD7 and TGF-β in rats with bleomycin-induced pulmonary fibrosis[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2007, 45(10): 1054 -1058 .
[8] ZHAO Ying, YAN Lei, ZHANG Hui, YU Peng, LI Ming-jiang, ZHAO Xing-bo. Expression of SPAG9 in patients with serous epithelial ovarian tumors[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2012, 50(2): 98 .
[9] WU Min,ZHAO Zhi-lun,WANG Jie-zhen. [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2006, 44(11): 1146 -1149 .
[10] . [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2008, 46(8): 828 -830 .