The four-microRNA signature identified by bioinformatics analysis predicts the prognosis of nasopharyngeal carcinoma patients

被引:21
作者
Zhang, Siwei [1 ,2 ]
Yue, Wenxing [1 ,2 ]
Xie, Yan [1 ,2 ]
Liu, Lingzhi [1 ,2 ]
Li, Shen [1 ,2 ]
Dang, Wei [1 ,2 ]
Xin, Shuyu [1 ,2 ]
Yang, Li [1 ,2 ]
Zhai, Xingyu [1 ,2 ]
Cao, Pengfei [1 ]
Lu, Jianhong [1 ,2 ]
机构
[1] Cent South Univ, Xiangya Hosp, Dept Hematol, NHC Key Lab Carcinogenesis, 87 Xiangya Rd, Changsha 410080, Hunan, Peoples R China
[2] Cent South Univ, Dept Microbiol, Sch Basic Med Sci, Changsha 410078, Hunan, Peoples R China
关键词
nasopharyngeal carcinoma; microRNAs; prognosis; microarray; weighted gene co-expression network analysis; pathway; TUMOR-SUPPRESSOR; DISTANT METASTASIS; MICRORNA EXPRESSION; INVASION; SURVIVAL; PTEN; ANGIOGENESIS; BIOMARKERS; SUBSEQUENT;
D O I
10.3892/or.2019.7316
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The aim of the present study was to identify microRNAs (miRNAs) that predict the prognosis of patients with nasopharyngeal carcinoma by integrated bioinformatics analysis. First, the original microarray dataset GSE32960, including 312 nasopharyngeal carcinomas and 18 normal samples, was downloaded from the Gene Expression Omnibus database. In addition, 46 differentially expressed miRNAs (DEMs) were screened. Then, four miRNAs, including hsa-miR-142-3p, hsa-miR-150, hsa-miR-29b, and hsa-miR-29c, were obtained as prognostic markers by combining univariate Cox regression analysis with weighted gene coexpression network analysis (WGCNA). Subsequently, the risk score of 312 NPC patients from the signature of miRNAs was calculated, and patients were divided into high-risk or low-risk groups. Notably, compared with patients with low-risk scores, high-risk groups had shorter disease-free survival (DFS), overall survival (OS), and distant metastasis-free survival (DMFS). Receiver operating characteristic curve (ROC) analysis indicated that the risk score was a very effective prognostic factor. Moreover, the Search Tool for the Database for Annotation, Visualization, and Integrated Discovery (DAVID), Cytoscape, starBase, and Retrieval of Interacting Genes database (STRING) were used to establish the miRNA-mRNA correlation network and the protein-protein interaction (PPI) network. In addition, the shared genes superimposing 888 protein-coding genes targeted by four hub miRNAs and 1,601 upregulated differentially expressed mRNAs accounted for 127 and were used for subsequent gene functional enrichment analysis. In particular, biological pathway analysis indicated that these genes mainly participate in some vital pathways related to cancer pathogenesis, such as the focal adhesion, PI3K/Akt, p53, and mTOR signalling pathways. In summary, the identification of NPC patients with a four-miRNA signature may increase the prognostic value and provide reference information for precision medicine.
引用
收藏
页码:1767 / 1780
页数:14
相关论文
共 51 条
[1]   VEGFA gene locus analysis across 80 human tumour types reveals gene amplification in several neoplastic entities [J].
Andreozzi, Mariacarla ;
Quagliata, Luca ;
Gsponer, Joel R. ;
Ruiz, Christian ;
Vuaroqueaux, Vincent ;
Eppenberger-Castori, Serenella ;
Tornillo, Luigi ;
Terracciano, Luigi M. .
ANGIOGENESIS, 2014, 17 (03) :519-527
[2]   MicroRNA-29b Inhibits Angiogenesis by Targeting VEGFA through the MAPK/ERK and PI3K/Akt Signaling Pathways in Endometrial Carcinoma [J].
Chen, Hong-Xia ;
Xu, Xiao-Xia ;
Zhang, Zhi ;
Tan, Bu-Zhen ;
Zhou, Xiao-Dong .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2017, 41 (03) :933-946
[3]   Clinicopathologic and prognostic significance of VEGF, JAK2 and STAT3 in patients with nasopharyngeal carcinoma [J].
Cheng, Jin-Zhang ;
Chen, Jun-Jun ;
Xue, Kai ;
Wang, Zong-Gui ;
Yu, Dan .
CANCER CELL INTERNATIONAL, 2018, 18
[4]   MicroRNAs in cancer - from research to therapy [J].
Cho, William C. S. .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2010, 1805 (02) :209-217
[5]   LEUKEMOID REACTION, BONE-MARROW INVASION, FEVER OF UNKNOWN ORIGIN, AND METASTATIC PATTERN IN THE NATURAL-HISTORY OF ADVANCED UNDIFFERENTIATED CARCINOMA OF NASOPHARYNGEAL TYPE - A REVIEW OF 255 CONSECUTIVE CASES [J].
CVITKOVIC, E ;
BACHOUCHI, M ;
BOUSSEN, H ;
BUSSON, P ;
ROUSSELET, G ;
MAHJOUBI, R ;
FLORES, P ;
TURSZ, T ;
ARMAND, JP ;
AZLI, N .
JOURNAL OF CLINICAL ONCOLOGY, 1993, 11 (12) :2434-2442
[6]   miR-216b suppresses tumor growth and invasion by targeting KRAS in nasopharyngeal carcinoma [J].
Deng, Min ;
Tang, Hailin ;
Zhou, Yanhong ;
Zhou, Ming ;
Xiong, Wei ;
Zheng, Ying ;
Ye, Qiurong ;
Zeng, Xi ;
Liao, Qianjin ;
Guo, Xiaofang ;
Li, Xiaoling ;
Ma, Jian ;
Li, Guiyuan .
JOURNAL OF CELL SCIENCE, 2011, 124 (17) :2997-3005
[7]   Research on miRNA-195 and target gene CDK6 in oral verrucous carcinoma [J].
Deng, Z. ;
Wang, Y. ;
Fang, X. ;
Yan, F. ;
Pan, H. ;
Gu, L. ;
Xie, C. ;
Li, Y. ;
Hu, Y. ;
Cao, Y. ;
Tang, Z. .
CANCER GENE THERAPY, 2017, 24 (07) :282-288
[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]   MicroRNA-29b Suppresses Tumor Angiogenesis, Invasion, and Metastasis by Regulating Matrix Metalloproteinase 2 Expression [J].
Fang, Jian-Hong ;
Zhou, Hui-Chao ;
Zeng, Chunxian ;
Yang, Jine ;
Liu, Yinglin ;
Huang, Xiuzhi ;
Zhang, Jing-Ping ;
Guan, Xin-Yuan ;
Zhuang, Shi-Mei .
HEPATOLOGY, 2011, 54 (05) :1729-1740
[10]   PTEN tumor suppressor regulates p53 protein levels and activity through phosphatase-dependent and -independent mechanisms [J].
Freeman, DJ ;
Li, AG ;
Wei, G ;
Li, HH ;
Kertesz, N ;
Lesche, R ;
Whale, AD ;
Martinez-Diaz, H ;
Rozengurt, N ;
Cardiff, RD ;
Liu, X ;
Wu, H .
CANCER CELL, 2003, 3 (02) :117-130