Identification of novel biomarkers and small molecule drugs in human colorectal cancer by microarray and bioinformatics analysis

被引:35
作者
Chen, Juan [1 ]
Wang, Ziheng [2 ,3 ]
Shen, Xianjuan [4 ]
Cui, Xiaopeng [5 ]
Guo, Yuehua [4 ]
机构
[1] Peoples Hosp Haian Cty, Lab Med Ctr, Nantong, Peoples R China
[2] Nantong Univ, Affiliated Hosp, Dept Clin Biobank, Nantong, Peoples R China
[3] Nantong Univ, Xinling Coll, Dept Med, Nantong, Peoples R China
[4] Nantong Univ, Affiliated Hosp, Res Ctr Clin Med, Nantong 226001, Peoples R China
[5] Nantong Univ, Affiliated Hosp, Dept Gen Surg, Nantong 226001, Peoples R China
来源
MOLECULAR GENETICS & GENOMIC MEDICINE | 2019年 / 7卷 / 07期
基金
中国国家自然科学基金;
关键词
colorectal cancer; bioinformatics; biomarker; drug; GENE-EXPRESSION; SUSCEPTIBILITY; CARCINOMA; ONTOLOGY; EXO1; AXIS;
D O I
10.1002/mgg3.713
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Background Colorectal cancer (CRC) is one of the most common malignant tumors. In the present study, the expression profile of human multistage colorectal mucosa tissues, including healthy, adenoma, and adenocarcinoma samples was downloaded to identify critical genes and potential drugs in CRC. Methods Expression profiles, GSE33113 and GSE44076, were integrated using bioinformatics methods. Differentially expressed genes (DEGs) were analyzed by R language. Functional enrichment analyses of the DEGs were performed using the Database for Annotation, visualization, and integrated discovery (DAVID) database. Then, the search tool for the retrieval of interacting genes (STRING) database and Cytoscape were used to construct a protein-protein interaction (PPI) network and identify hub genes. Subsequently, survival analysis was performed among the key genes using Gene Expression Profiling Interactive Analysis (GEPIA). Connectivity Map (CMap) was used to query potential drugs for CRC. Results A total of 428 upregulated genes and 751 downregulated genes in CRC were identified. The functional changes of these DEGs were mainly associated with cell cycle, oocyte meiosis, DNA replication, p53 signaling pathway, and progesterone-mediated oocyte maturation. A PPI network was identified by STRING with 482 nodes and 2,368 edges. Survival analysis revealed that high mRNA expression of AURKA, CCNB1, CCNF, and EXO1 was significantly associated with longer overall survival. Moreover, CMap predicted a panel of small molecules as possible adjuvant drugs to treat CRC. Conclusion Our study found key dysregulated genes involved in CRC and potential drugs to combat it, which may provide novel insights and potential biomarkers for prognosis, as well as providing new CRC treatments.
引用
收藏
页数:15
相关论文
共 49 条
[1]   Identification of prognostic genes in colorectal cancer through transcription profiling of multi-stage carcinogenesis [J].
An, Ning ;
Zhao, Chen ;
Yu, Zhuang ;
Yang, Xue .
ONCOLOGY LETTERS, 2019, 17 (01) :432-441
[2]  
[Anonymous], 2003, GENOME BIOL
[3]   Gene Ontology: tool for the unification of biology [J].
Ashburner, M ;
Ball, CA ;
Blake, JA ;
Botstein, D ;
Butler, H ;
Cherry, JM ;
Davis, AP ;
Dolinski, K ;
Dwight, SS ;
Eppig, JT ;
Harris, MA ;
Hill, DP ;
Issel-Tarver, L ;
Kasarskis, A ;
Lewis, S ;
Matese, JC ;
Richardson, JE ;
Ringwald, M ;
Rubin, GM ;
Sherlock, G .
NATURE GENETICS, 2000, 25 (01) :25-29
[4]   MultiContrast Delayed Enhancement (MCODE) improves detection of subendocardial myocardial infarction by late gadolinium enhancement cardiovascular magnetic resonance: a clinical validation study [J].
Bandettini, W. Patricia ;
Kellman, Peter ;
Mancini, Christine ;
Booker, Oscar Julian ;
Vasu, Sujethra ;
Leung, Steve W. ;
Wilson, Joel R. ;
Shanbhag, Sujata M. ;
Chen, Marcus Y. ;
Arai, Andrew E. .
JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE, 2012, 14
[5]   Single-Nucleotide Polymorphism of the Exo1 Gene: Association with Gastric Cancer Susceptibility and Interaction with Smoking in Taiwan [J].
Bau, Da-Tian ;
Wang, Hwei-Chung ;
Liu, Chiu-Shong ;
Chang, Chia-Lin ;
Chiang, Su-Yin ;
Wang, Rou-Fen ;
Tsai, Chia-Wen ;
Lo, Yen-Li ;
Hsiung, Chao A. ;
Lin, Cheng-Chieh ;
Huang, Chih-Yang .
CHINESE JOURNAL OF PHYSIOLOGY, 2009, 52 (06) :411-418
[6]   Genes overexpressed in different human solid cancers exhibit different tissue-specific expression profiles [J].
Bock-Axelsen, Jacob ;
Lotem, Joseph ;
Sachs, Leo ;
Dornany, Eytan .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (32) :13122-13127
[7]   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
[8]   Over-expression of AURKA, SKA3 and DSN1 contributes to colorectal adenoma to carcinoma progression [J].
Chuang, Tzu-Po ;
Wang, Jaw-Yuan ;
Jao, Shu-Wen ;
Wu, Chang-Chieh ;
Chen, Jiann-Hwa ;
Hsiao, Koung-Hung ;
Lin, Chung-Yen ;
Chen, Shu-Hwa ;
Su, Sheng-Yao ;
Chen, Ying-Ju ;
Chen, Yuan-Tsong ;
Wu, Deng-Chyang ;
Li, Ling-Hui .
ONCOTARGET, 2016, 7 (29) :45803-45818
[9]   Identification of candidate susceptibility genes for colorectal cancer through eQTL analysis [J].
Closa, Adria ;
Cordero, David ;
Sanz-Pamplona, Rebeca ;
Sole, Xavier ;
Crous-Bou, Marta ;
Pare-Brunet, Laia ;
Berenguer, Antoni ;
Guino, Elisabet ;
Lopez-Doriga, Adriana ;
Guardiola, Jordi ;
Biondo, Sebastiano ;
Salazar, Ramon ;
Moreno, Victor .
CARCINOGENESIS, 2014, 35 (09) :2039-2046
[10]   Large differences in global transcriptional regulatory programs of normal and tumor colon cells [J].
Cordero, David ;
Sole, Xavier ;
Crous-Bou, Marta ;
Sanz-Pamplona, Rebeca ;
Pare-Brunet, Laia ;
Guino, Elisabet ;
Olivares, David ;
Berenguer, Antonio ;
Santos, Cristina ;
Salazar, Ramon ;
Biondo, Sebastiano ;
Moreno, Victor .
BMC CANCER, 2014, 14