Novel prognostic biomarkers of gastric cancer based on gene expression microarray: COL12A1, GSTA3, FGA and FGG

被引:51
作者
Duan, Shijie [1 ]
Gong, Baocheng [1 ]
Wang, Pengliang [1 ]
Huang, Hanwei [1 ]
Luo, Lei [1 ]
Liu, Funan [1 ]
机构
[1] China Med Univ, Affiliated Hosp 1, Dept Surg Oncol, 155 Nanjing North St, Shenyang 110001, Liaoning, Peoples R China
基金
中国国家自然科学基金;
关键词
gastric cancer; biomarker; differentially expressed genes; PPI network; modules; KM plotter; INTRATUMOR HETEROGENEITY; FIBRINOGEN; CELLS; HYPERFIBRINOGENEMIA; POLYMORPHISMS; METASTASIS; CEA;
D O I
10.3892/mmr.2018.9368
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-associated mortality in the world. However, its mechanisms of occurrence and development have not been clearly elucidated. Furthermore, there is no effective tumor marker for GC. Using DNA microarray analysis, the present study revealed genetic alterations, screened out core genes as novel markers and discovered pathways for potential therapeutic targets. Differentially expressed genes (DEGs) between GC and adjacent normal tissues were identified, followed by pathway enrichment analysis of DEGs. Next, the protein-protein interaction (PPI) network of DEGs was built and visualized. Analyses of modules in the PPI network were then performed to identify the functional core genes. Finally, survival analysis of core genes was conducted. A total of 256 genes were identified as DEGs between the GC samples and normal samples, including 169 downregulated and 87 upregulated genes. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, the present study identified a total of 143 GO terms and 21 pathways. Six clusters of functional modules were identified, and the genes associated with these modules were screened out as the functional core genes. Certain core genes, including collagen type 12 1 chain (COL12A1), glutathione S-transferase 3 (GSTA3), fibrinogen chain (FGA) and fibrinogen chain (FGG), were the first reported to be associated with GC. Survival analysis suggested that these four genes, COL12A1 (P=0.002), GSTA3 (P=3.4x10(-6)), FGA (P=0.00075) and FGG (P=1.4x10-5), were significant poor prognostic factors and therefore, potential targets to improve diagnosis, optimize chemotherapy and predict prognostic outcomes.
引用
收藏
页码:3727 / 3736
页数:10
相关论文
共 55 条
[1]   Global surveillance of cancer survival 1995-2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2) [J].
Allemani, Claudia ;
Weir, Hannah K. ;
Carreira, Helena ;
Harewood, Rhea ;
Spika, Devon ;
Wang, Xiao-Si ;
Bannon, Finian ;
Ahn, Jane V. ;
Johnson, Christopher J. ;
Bonaventure, Audrey ;
Marcos-Gragera, Rafael ;
Stiller, Charles ;
Azevedo e Silva, Gulnar ;
Chen, Wan-Qing ;
Ogunbiyi, Olufemi J. ;
Rachet, Bernard ;
Soeberg, Matthew J. ;
You, Hui ;
Matsuda, Tomohiro ;
Bielska-Lasota, Magdalena ;
Storm, Hans ;
Tucker, Thomas C. ;
Coleman, Michel P. .
LANCET, 2015, 385 (9972) :977-1010
[2]   Role for Daple in non-canonical Wnt signaling during gastric cancer invasion and metastasis [J].
Ara, Hosne ;
Takagishi, Maki ;
Enomoto, Atsushi ;
Asai, Masato ;
Ushida, Kaori ;
Asai, Naoya ;
Shimoyama, Yoshie ;
Kaibuchi, Kozo ;
Kodera, Yasuhiro ;
Takahashi, Masahide .
CANCER SCIENCE, 2016, 107 (02) :133-139
[3]  
Bang YJ, 2010, LANCET, V376, P1302
[4]   Comprehensive molecular characterization of gastric adenocarcinoma [J].
Bass, Adam J. ;
Thorsson, Vesteinn ;
Shmulevich, Ilya ;
Reynolds, Sheila M. ;
Miller, Michael ;
Bernard, Brady ;
Hinoue, Toshinori ;
Laird, Peter W. ;
Curtis, Christina ;
Shen, Hui ;
Weisenberger, Daniel J. ;
Schultz, Nikolaus ;
Shen, Ronglai ;
Weinhold, Nils ;
Keiser, David P. ;
Bowlby, Reanne ;
Sipahimalani, Payal ;
Cherniack, Andrew D. ;
Getz, Gad ;
Liu, Yingchun ;
Noble, Michael S. ;
Pedamallu, Chandra ;
Sougnez, Carrie ;
Taylor-Weiner, Amaro ;
Akbani, Rehan ;
Lee, Ju-Seog ;
Liu, Wenbin ;
Mills, Gordon B. ;
Yang, Da ;
Zhang, Wei ;
Pantazi, Angeliki ;
Parfenov, Michael ;
Gulley, Margaret ;
Piazuelo, M. Blanca ;
Schneider, Barbara G. ;
Kim, Jihun ;
Boussioutas, Alex ;
Sheth, Margi ;
Demchok, John A. ;
Rabkin, Charles S. ;
Willis, Joseph E. ;
Ng, Sam ;
Garman, Katherine ;
Beer, David G. ;
Pennathur, Arjun ;
Raphael, Benjamin J. ;
Wu, Hsin-Ta ;
Odze, Robert ;
Kim, Hark K. ;
Bowen, Jay .
NATURE, 2014, 513 (7517) :202-209
[5]   Expression Profiling of Stem Cell-Related Genes in Neoadjuvant-Treated Gastric Cancer: A NOTCH2, GSK3B and β-catenin Gene Signature Predicts Survival [J].
Bauer, Lukas ;
Langer, Rupert ;
Becker, Karen ;
Hapfelmeier, Alexander ;
Ott, Katja ;
Novotny, Alexander ;
Hoefler, Heinz ;
Keller, Gisela .
PLOS ONE, 2012, 7 (09)
[6]   Adjustment of systematic microarray data biases [J].
Benito, M ;
Parker, J ;
Du, Q ;
Wu, JY ;
Xang, D ;
Perou, CM ;
Marron, JS .
BIOINFORMATICS, 2004, 20 (01) :105-114
[7]   Recent patterns in gastric cancer: A global overview [J].
Bertuccio, Paola ;
Chatenoud, Liliane ;
Levi, Fabio ;
Praud, Delphine ;
Ferlay, Jacques ;
Negri, Eva ;
Malvezzi, Matteo ;
La Vecchia, Carlo .
INTERNATIONAL JOURNAL OF CANCER, 2009, 125 (03) :666-673
[8]   Fibrinogen γ overexpression in pancreatic cancer identified by large-scale proteomic analysis of serum samples [J].
Bloomston, M ;
Zhou, JX ;
Rosemurgy, AS ;
Frankel, W ;
Muro-Cacho, CA ;
Yeatman, TJ .
CANCER RESEARCH, 2006, 66 (05) :2592-2599
[9]   Positional expression profiling indicates candidate genes in deletion hotspots of hepatocellular carcinoma [J].
Chan, Kathy Y-Y ;
Lai, Paul B-S ;
Squire, Jeremy A. ;
Beheshti, Ben ;
Wong, Navy L-Y ;
Sy, Shirley M-H ;
Wong, Nathalie .
MODERN PATHOLOGY, 2006, 19 (12) :1546-1554
[10]   Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy [J].
Chang, F ;
Lee, JT ;
Navolanic, PM ;
Steelman, LS ;
Shelton, JG ;
Blalock, WL ;
Franklin, RA ;
McCubrey, JA .
LEUKEMIA, 2003, 17 (03) :590-603