Identification of hub genes and therapeutic drugs in esophageal squamous cell carcinoma based on integrated bioinformatics strategy

被引:25
作者
Yang, Wanli [1 ,2 ]
Zhao, Xinhui [1 ,2 ]
Han, Yu [3 ]
Duan, Lili [1 ,2 ]
Lu, Xin [4 ]
Wang, Xiaoqian [1 ,2 ]
Zhang, Yujie [1 ,2 ]
Zhou, Wei [1 ,2 ]
Liu, Jinqiang [1 ,2 ]
Zhang, Hongwei [1 ,2 ]
Zhao, Qingchuan [1 ,2 ]
Hong, Liu [1 ,2 ]
Fan, Daiming [1 ,2 ]
机构
[1] Fourth Mil Med Univ, State Key Lab Canc Biol, Natl Clin Res Ctr Digest Dis, Xian, Shaanxi, Peoples R China
[2] Fourth Mil Med Univ, Xijing Hosp Digest Dis, Xian, Shaanxi, Peoples R China
[3] Fourth Mil Med Univ, Dept Otolaryngol, Xijing Hosp, Xian, Shaanxi, Peoples R China
[4] Xi An Jiao Tong Univ, Sch Life Sci & Technol, Xian, Shaanxi, Peoples R China
关键词
Esophageal squamous cell carcinoma; Bioinformatics; Hub genes; Cell cycle; Differentially expressed genes; Drug; EXTRACELLULAR-MATRIX; KEY GENES; CANCER; EXPRESSION; PROLIFERATION; METASTASIS; PATHWAYS; GROWTH; CYCLE; PROGRESSION;
D O I
10.1186/s12935-019-0854-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundEsophageal squamous cell carcinoma (ESCC) is one of leading malignant cancers of gastrointestinal tract worldwide. Until now, the involved mechanisms during the development of ESCC are largely unknown. This study aims to explore the driven-genes and biological pathways in ESCC.MethodsmRNA expression datasets of GSE29001, GSE20347, GSE100942, and GSE38129, containing 63 pairs of ESCC and non-tumor tissues data, were integrated and deeply analyzed. The bioinformatics approaches include identification of differentially expressed genes (DEGs) and hub genes, gene ontology (GO) terms analysis and biological pathway enrichment analysis, construction and analysis of protein-protein interaction (PPI) network, and miRNA-gene network construction. Subsequently, GEPIA2 database and qPCR assay were utilized to validate the expression of hub genes. DGIdb database was performed to search the candidate drugs for ESCC.ResultsFinally, 120 upregulated and 26 downregulated DEGs were identified. The functional enrichment of DEGs in ESCC were mainly correlated with cell cycle, DNA replication, deleted in colorectal cancer (DCC) mediated attractive signaling pathway, and Netrin-1 signaling pathway. The PPI network was constructed using STRING software with 146 nodes and 2392 edges. The most significant three modules in PPI were filtered and analyzed. Totally ten genes were selected and considered as the hub genes and nuclear division cycle 80 (NDC80) was closely related to the survival of ESCC patients. DGIdb database predicted 33 small molecules as the possible drugs for treating ESCC.ConclusionsIn summary, the data may provide new insights into ESCC pathogenesis and treatments. The candidate drugs may improve the efficiency of personalized therapy in future.
引用
收藏
页数:15
相关论文
共 65 条
[1]  
[Anonymous], NUCLEIC ACIDS RES
[2]  
Atwal Mandeep, 2017, Mol Pharmacol, V91, P49
[3]   NCBI GEO: archive for functional genomics data sets-update [J].
Barrett, Tanya ;
Wilhite, Stephen E. ;
Ledoux, Pierre ;
Evangelista, Carlos ;
Kim, Irene F. ;
Tomashevsky, Maxim ;
Marshall, Kimberly A. ;
Phillippy, Katherine H. ;
Sherman, Patti M. ;
Holko, Michelle ;
Yefanov, Andrey ;
Lee, Hyeseung ;
Zhang, Naigong ;
Robertson, Cynthia L. ;
Serova, Nadezhda ;
Davis, Sean ;
Soboleva, Alexandra .
NUCLEIC ACIDS RESEARCH, 2013, 41 (D1) :D991-D995
[4]   Remodelling the extracellular matrix in development and disease [J].
Bonnans, Caroline ;
Chou, Jonathan ;
Werb, Zena .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2014, 15 (12) :786-801
[5]   The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data [J].
Cerami, Ethan ;
Gao, Jianjiong ;
Dogrusoz, Ugur ;
Gross, Benjamin E. ;
Sumer, Selcuk Onur ;
Aksoy, Buelent Arman ;
Jacobsen, Anders ;
Byrne, Caitlin J. ;
Heuer, Michael L. ;
Larsson, Erik ;
Antipin, Yevgeniy ;
Reva, Boris ;
Goldberg, Arthur P. ;
Sander, Chris ;
Schultz, Nikolaus .
CANCER DISCOVERY, 2012, 2 (05) :401-404
[6]   Dasatinib enhances cisplatin sensitivity in human esophageal squamous cell carcinoma (ESCC) cells via suppression of PI3K/AKT and Stat3 pathways [J].
Chen, Jie ;
Lan, Tian ;
Zhang, Weimin ;
Dong, Lijia ;
Kang, Nan ;
Fu, Ming ;
Liu, Bing ;
Liu, Kangtai ;
Zhang, Cuixiang ;
Hou, Jincai ;
Zhan, Qimin .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2015, 575 :38-45
[7]  
Cotto Kelsy C, 2018, Nucleic Acids Res, V46, pD1068, DOI 10.1093/nar/gkx1143
[8]   DAVID: Database for annotation, visualization, and integrated discovery [J].
Dennis, G ;
Sherman, BT ;
Hosack, DA ;
Yang, J ;
Gao, W ;
Lane, HC ;
Lempicki, RA .
GENOME BIOLOGY, 2003, 4 (09)
[9]   Rebooting the collagen gel: Artificial hydrogels for the study of epithelial mesenchymal transformation [J].
Dettman, Robert W. ;
Simon, Hans-Georg .
DEVELOPMENTAL DYNAMICS, 2018, 247 (03) :332-339
[10]   Targeting the cell cycle in esophageal adenocarcinoma: An adjunct to anticancer treatment [J].
Dibb, Martyn ;
Ang, Yeng S. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2011, 17 (16) :2063-2069