Prognostic Genes of Breast Cancer Identified by Gene Co-expression Network Analysis

被引:196
作者
Tang, Jianing [1 ]
Kong, Deguang [2 ]
Cui, Qiuxia [1 ]
Wang, Kun [3 ]
Zhang, Dan [3 ]
Gong, Yan [4 ]
Wu, Gaosong [1 ]
机构
[1] Wuhan Univ, Zhongnan Hosp, Dept Thyroid & Breast Surg, Wuhan, Hubei, Peoples R China
[2] Wuhan Univ, Zhongnan Hosp, Dept Gen Surg, Wuhan, Hubei, Peoples R China
[3] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Thyroid & Breast Surg, Wuhan, Hubei, Peoples R China
[4] Wuhan Univ, Zhongnan Hosp, Dept Biol Repositories, Wuhan, Hubei, Peoples R China
基金
英国科研创新办公室;
关键词
breast cancer; weighted gene co-expression network analysis (WGCNA); prognosis; GEO; TCGA; ENHANCED EXPRESSION; CELL-PROLIFERATION; KEY GENES; SURVIVAL; PROTEIN; GROWTH; TPX2; OVEREXPRESSION; PREDICTION; BIOMARKER;
D O I
10.3389/fonc.2018.00374
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Breast cancer is one of the most common malignancies. The molecular mechanisms of its pathogenesis are still to be investigated. The aim of this study was to identify the potential genes associated with the progression of breast cancer. Weighted gene co-expression network analysis (WGCNA) was used to construct free-scale gene co-expression networks to explore the associations between gene sets and clinical features, and to identify candidate biomarkers. The gene expression profiles of GSE1561 were selected from the Gene Expression Omnibus (GEO) database. RNA-seq data and clinical information of breast cancer from TCGA were used for validation. A total of 18 modules were identified via the average linkage hierarchical clustering. In the significant module (R-2 = 0.48), 42 network hub genes were identified. Based on the Cancer Genome Atlas (TCGA) data, 5 hub genes (CCNB2, FBXO5, KIF4A, MCM10, and TPX2) were correlated with poor prognosis. Receiver operating characteristic (ROC) curve validated that the mRNA levels of these 5 genes exhibited excellent diagnostic efficiency for normal and tumor tissues. In addition, the protein levels of these 5 genes were also significantly higher in tumor tissues compared with normal tissues. Among them, CCNB2, KIF4A, and TPX2 were further upregulated in advanced tumor stage. In conclusion, 5 candidate biomarkers were identified for further basic and clinical research on breast cancer with co-expression network analysis.
引用
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页数:13
相关论文
共 39 条
[1]  
Braden AM, 2014, CURR PHARM DESIGN, V20, P4879
[2]   Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis [J].
Clarke, Colin ;
Madden, Stephen F. ;
Doolan, Padraig ;
Aherne, Sinead T. ;
Joyce, Helena ;
O'Driscoll, Lorraine ;
Gallagher, William M. ;
Hennessy, Bryan T. ;
Moriarty, Michael ;
Crown, John ;
Kennedy, Susan ;
Clynes, Martin .
CARCINOGENESIS, 2013, 34 (10) :2300-2308
[3]   Identification of molecular apocrine breast tumours by microarray analysis [J].
Farmer, P ;
Bonnefoi, H ;
Becette, V ;
Tubiana-Hulin, M ;
Fumoleau, P ;
Larsimont, D ;
MacGrogan, G ;
Bergh, J ;
Cameron, D ;
Goldstein, D ;
Duss, S ;
Nicoulaz, AL ;
Brisken, C ;
Fiche, M ;
Delorenzi, M ;
Iggo, R .
ONCOGENE, 2005, 24 (29) :4660-4671
[4]   Functional Analysis of Prognostic Gene Expression Network Genes in Metastatic Breast Cancer Models [J].
Geiger, Thomas R. ;
Ngoc-Han Ha ;
Faraji, Farhoud ;
Michael, Helen T. ;
Rodriguez, Loren ;
Walker, Renard C. ;
Green, Jeffery E. ;
Simpson, R. Mark ;
Hunter, Kent W. .
PLOS ONE, 2014, 9 (11)
[5]   Lapatinib plus capecitabine for HER2-positive advanced breast cancer [J].
Geyer, Charles E. ;
Forster, John ;
Lindquist, Deborah ;
Chan, Stephen ;
Romieu, C. Gilles ;
Pienkowski, Tadeusz ;
Jagiello-Gruszfeld, Agnieszka ;
Crown, John ;
Chan, Arlene ;
Kaufman, Bella ;
Skarlos, Dimosthenis ;
Campone, Mario ;
Davidson, Neville ;
Berger, Mark ;
Oliva, Cristina ;
Rubin, Stephen D. ;
Stein, Steven ;
Cameron, David .
NEW ENGLAND JOURNAL OF MEDICINE, 2006, 355 (26) :2733-2743
[6]   Enhanced expression of early mitotic inhibitor-1 predicts a poor prognosis in esophageal squamous cell carcinoma patients [J].
Guan, Chengqi ;
Zhang, Jianfeng ;
Zhang, Jianguo ;
Shi, Hui ;
Ni, Runzhou .
ONCOLOGY LETTERS, 2016, 12 (01) :114-120
[7]   Emi1 protein accumulation implicates misregulation of the anaphase promoting complex/cyclosome pathway in ovarian clear cell carcinoma [J].
Guetgemann, Ines ;
Lehman, Norman L. ;
Jackson, Peter K. ;
Longacre, Teri A. .
MODERN PATHOLOGY, 2008, 21 (04) :445-454
[8]   Identification of key genes associated with bladder cancer using gene expression profiles [J].
Han, Yuping ;
Jin, Xuefei ;
Zhou, Hui ;
Liu, Bin .
ONCOLOGY LETTERS, 2018, 15 (01) :297-303
[9]   Identification of genes associated with castration-resistant prostate cancer by gene expression profile analysis [J].
Huang, Chui Guo ;
Li, Feng Xi ;
Pan, Song ;
Xu, Chang Bao ;
Dai, Jun Qiang ;
Zhao, Xing Hua .
MOLECULAR MEDICINE REPORTS, 2017, 16 (05) :6803-6813
[10]   Upregulation of kinesin family member 4A enhanced cell proliferation via activation of Akt signaling and predicted a poor prognosis in hepatocellular carcinoma [J].
Huang, Yanlin ;
Wang, Hongbo ;
Lian, Yifan ;
Wu, Xiaojuan ;
Zhou, Liang ;
Wang, Jialiang ;
Deng, Meihai ;
Huang, Yuehua .
CELL DEATH & DISEASE, 2018, 9