The identification of key biomarkers in patients with lung adenocarcinoma based on bioinformatics

被引:26
作者
Ni, Kewei [1 ,2 ]
Sun, Gaozhong [1 ,2 ]
机构
[1] Zhejiang Prov Peoples Hosp, Dept Cardiothorac Surg, Hangzhou, Zhejiang, Peoples R China
[2] Peoples Hosp, Hangzhou Med Coll, Hangzhou, Zhejiang, Peoples R China
关键词
Lung adenocarcinoma; biomarkers; bioinformatics analysis; CANCER; EXPRESSION; METASTASIS; MECHANISMS; DIAGNOSIS; PATHWAY; CHINESE; RISK;
D O I
10.3934/mbe.2019384
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Lung adenocarcinoma (LUAD) is one of the leading causes of cancer death globally. This study aims to investigate the underlying mechanisms implicated with LUAD and identify the key biomarkers. LUAD-associated gene expression dataset (GSE10072) was obtained from GEO database. Based on the GEO2R tool, we screened the differentially expressed genes (DEGs) between the patients with LUAD and normal individuals. Subsequently, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were employed to find out the enriched pathways of these DEGs. Meanwhile, a protein-protein interaction (PPI) network was also employed to construct to visualize the interactions of these DEGs. Finally, the survival analysis of the top5 up-regulated and top5 down-regulated genes were conducted via GEPIA, aiming to figure out their potential effects on LUAD. In our study, a total of 856 DEGs were captured, including 559 up-regulated genes and 297 down-regulated genes. Among these DEGs, the top5 up-regulated genes were AGER, SFTPC, FABP4, CYP4B1 and WIF1 while the top5 down-regulated genes were GREM1, SPINK1, MMP1, COL11A1 and SPP1. GO analysis disclosed that these DEGs were mainly enriched in DNA synthesis, cell adhesion, signal transduction and cell apoptosis. KEGG analysis unveiled that the enriched pathway included pathways in cancer, PI3K/Akt signaling pathway, MAPK signaling pathway and cell cycle. Survival analysis showed that the expression level of ZG16 may correlate with the prognosis of LUAD patients. Furthermore, according to the connectivity degree of these DEGs, we selected the top15 hub genes, namely IL6, MMP9, EDN1, FOS, CDK1, CDH1, BIRC5, VWF, UBE2C, CDKN3, CDKN2A, CD34, AURKA, CCNB2 and EGR1, which were expected to be promising therapeutic target in LUAD. In conclusion, our study disclosed potential biomarkers and candidate targets in LUAD, which could be helpful to the diagnosis and treatment of LUAD.
引用
收藏
页码:7671 / 7687
页数:17
相关论文
共 36 条
[1]   Staging of Non-Small-Cell Lung Cancer [J].
Akhurst, Tim .
PET CLINICS, 2018, 13 (01) :1-+
[2]  
[Anonymous], 2003, GENOME BIOL
[3]   Tissue microarrays: bridging the gap between research and the clinic [J].
Braunschweig, T ;
Chung, JY ;
Hewitt, SM .
EXPERT REVIEW OF PROTEOMICS, 2005, 2 (03) :325-336
[4]   Genomic Analysis of Tumor Microenvironment Immune Types across 14 Solid Cancer Types: Immunotherapeutic Implications [J].
Chen, Yu-Pei ;
Zhang, Yu ;
Lv, Jia-Wei ;
Li, Ying-Qin ;
Wang, Ya-Qin ;
He, Qing-Mei ;
Yang, Xiao-Jing ;
Sun, Ying ;
Mao, Yan-Ping ;
Yun, Jing-Ping ;
Liu, Na ;
Ma, Jun .
THERANOSTICS, 2017, 7 (14) :3585-3594
[5]   PARP1 enhances lung adenocarcinoma metastasis by novel mechanisms independent of DNA repair [J].
Choi, E-B ;
Yang, A-Y ;
Kim, S. C. ;
Lee, J. ;
Choi, J. K. ;
Choi, C. ;
Kim, M-Y .
ONCOGENE, 2016, 35 (35) :4569-4579
[6]   Towards automatic pulmonary nodule management in lung cancer screening with deep learning [J].
Ciompi, Francesco ;
Chung, Kaman ;
van Riel, Sarah J. ;
Setio, Arnaud Arindra Adiyoso ;
Gerke, Paul K. ;
Jacobs, Colin ;
Scholten, Ernst Th. ;
Schaefer-Prokop, Cornelia ;
Wille, Mathilde M. W. ;
Marchiano, Alfonso ;
Pastorino, Ugo ;
Prokop, Mathias ;
van Ginneken, Bram .
SCIENTIFIC REPORTS, 2017, 7
[7]   Comprehensive molecular profiling of lung adenocarcinoma [J].
Collisson, Eric A. ;
Campbell, Joshua D. ;
Brooks, Angela N. ;
Berger, Alice H. ;
Lee, William ;
Chmielecki, Juliann ;
Beer, David G. ;
Cope, Leslie ;
Creighton, Chad J. ;
Danilova, Ludmila ;
Ding, Li ;
Getz, Gad ;
Hammerman, Peter S. ;
Hayes, D. Neil ;
Hernandez, Bryan ;
Herman, James G. ;
Heymach, John V. ;
Jurisica, Igor ;
Kucherlapati, Raju ;
Kwiatkowski, David ;
Ladanyi, Marc ;
Robertson, Gordon ;
Schultz, Nikolaus ;
Shen, Ronglai ;
Sinha, Rileen ;
Sougnez, Carrie ;
Tsao, Ming-Sound ;
Travis, William D. ;
Weinstein, John N. ;
Wigle, Dennis A. ;
Wilkerson, Matthew D. ;
Chu, Andy ;
Cherniack, Andrew D. ;
Hadjipanayis, Angela ;
Rosenberg, Mara ;
Weisenberger, Daniel J. ;
Laird, Peter W. ;
Radenbaugh, Amie ;
Ma, Singer ;
Stuart, Joshua M. ;
Byers, Lauren Averett ;
Baylin, Stephen B. ;
Govindan, Ramaswamy ;
Meyerson, Matthew ;
Rosenberg, Mara ;
Gabriel, Stacey B. ;
Cibulskis, Kristian ;
Sougnez, Carrie ;
Kim, Jaegil ;
Stewart, Chip .
NATURE, 2014, 511 (7511) :543-550
[8]   New KEGG pathway-based interpretable features for classifying ageing-related mouse proteins [J].
Fabris, Fabio ;
Freitas, Alex A. .
BIOINFORMATICS, 2016, 32 (19) :2988-2995
[9]   Proteomic profiling of lung adenocarcinoma indicates heightened DNA repair, antioxidant mechanisms and identifies LASP1 as a potential negative predictor of survival [J].
Fahrmann, Johannes F. ;
Grapov, Dmitry ;
Phinney, Brett S. ;
Stroble, Carol ;
DeFelice, Brian C. ;
Rom, William ;
Gandara, David R. ;
Zhang, Yanhong ;
Fiehn, Oliver ;
Pass, Harvey ;
Miyamoto, Suzanne .
CLINICAL PROTEOMICS, 2016, 13 :1-12
[10]   Genetic predisposition to lung adenocarcinoma among never-smoking Chinese with different epidermal growth factor receptor mutation status [J].
Han, Li ;
Lee, Cheuk-Kwong ;
Pang, Herbert ;
Chan, Hong-Tou ;
Lo, Iek-Long ;
Lam, Sze-Kwan ;
Cheong, Tak-Hong ;
Ho, James Chung-Man .
LUNG CANCER, 2017, 114 :79-89