Identification of key genes associated with gastric cancer based on DNA microarray data

The present study aimed to identify genes with a differential pattern of expression in gastric cancer (GC), and to find novel molecular biomarkers for GC diagnosis and therapeutic treatment. The gene expression profile of GSE19826, including 12 GC samples and 15 normal controls, was downloaded from the Gene Expression Omnibus database. Differentially-expressed genes (DEGs) were screened in the GC samples compared with the normal controls. Two-way hierarchical clustering of DEGs was performed to distinguish the normal controls from the GC samples. The co-expression coefficient was analyzed among the DEGs using the data from COXPRESdb. The gene co-expression network was constructed based on the DEGs using Cytoscape software, and modules in the network were analyzed by ClusterOne and Bingo. Furthermore, enrichment analysis of the DEGs in the modules was performed using the Database for Annotation, Visualization and Integrated Discovery. In total, 596 DEGs in the GC samples and 57 co-expression gene pairs were identified. A total of 7 genes were enriched in the same module, for which the function was phosphate transport and which was annotated to participate in the extracellular matrix-receptor interaction pathway. These genes were collagen, type VI, α3 (COL6A3), COL1A2, COL1A1, COL5A2, thrombospondin 2, COL11A1 and COL5A1. Overall, the present study identified several biomarkers for GC using the gene expression profiling of human GC samples. The COL family is a promising prognostic marker for GC. Gene expression products represent candidate biomarkers endowed with great potential for the early screening and therapy of GC patients.

[1]  P. Pfeiffer,et al.  Phase II study of short-time oxaliplatin, capecitabine and epirubicin (EXE) as first-line therapy in patients with non-resectable gastric cancer , 2008, British Journal of Cancer.

[2]  Elena Deza,et al.  Encyclopedia of Distances , 2014 .

[3]  Ross Ihaka,et al.  Gentleman R: R: A language for data analysis and graphics , 1996 .

[4]  Hongyu Diao,et al.  Gene Expression Profiling Combined with Bioinformatics Analysis Identify Biomarkers for Parkinson Disease , 2012, PloS one.

[5]  J. Si,et al.  Collagen: a possible prediction mark for gastric cancer. , 2009, Medical hypotheses.

[6]  Gary D. Bader,et al.  An automated method for finding molecular complexes in large protein interaction networks , 2003, BMC Bioinformatics.

[7]  Trey Ideker,et al.  Cytoscape 2.8: new features for data integration and network visualization , 2010, Bioinform..

[8]  Gábor J. Székely,et al.  Hierarchical Clustering via Joint Between-Within Distances: Extending Ward's Minimum Variance Method , 2005, J. Classif..

[9]  J. Davis Bioinformatics and Computational Biology Solutions Using R and Bioconductor , 2007 .

[10]  P. Liu,et al.  Bioinformatics analysis with graph-based clustering to detect gastric cancer-related pathways. , 2012, Genetics and molecular research : GMR.

[11]  Misako Sato,et al.  Heparanase: A Key Enzyme in Invasion and Metastasis of Gastric Carcinoma , 2002, Modern Pathology.

[12]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[13]  Dennis B. Troup,et al.  NCBI GEO: mining tens of millions of expression profiles—database and tools update , 2006, Nucleic Acids Res..

[14]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[15]  Ming-Tsan Lin,et al.  Gene expression profiling of gastric cancer by microarray combined with laser capture microdissection. , 2005, World journal of gastroenterology.

[16]  H. Simon,et al.  Pdlim7 (LMP4) regulation of Tbx5 specifies zebrafish heart atrio-ventricular boundary and valve formation. , 2010, Developmental biology.

[17]  C. V. D. van de Velde,et al.  Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. , 2006, The New England journal of medicine.

[18]  J. R. Kelley,et al.  Gastric cancer epidemiology and risk factors. , 2003, Journal of clinical epidemiology.

[19]  A. Ullrich,et al.  The discovery of receptor tyrosine kinases: targets for cancer therapy , 2004, Nature Reviews Cancer.

[20]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[21]  A. Reiner-Benaim FDR Control by the BH Procedure for Two‐Sided Correlated Tests with Implications to Gene Expression Data Analysis , 2007, Biometrical journal. Biometrische Zeitschrift.

[22]  P. Seeburg,et al.  Cloning of a human RNA editing deaminase (ADARB1) of glutamate receptors that maps to chromosome 21q22.3. , 1997, Genomics.

[23]  Kengo Kinoshita,et al.  COXPRESdb: a database of comparative gene coexpression networks of eleven species for mammals , 2012, Nucleic Acids Res..

[24]  K. Pienta,et al.  E-cadherin expression in prostate cancer: a broad survey using high-density tissue microarray technology. , 2001, Human pathology.

[25]  Wei Li,et al.  Plasma microRNAs, miR-223, miR-21 and miR-218, as Novel Potential Biomarkers for Gastric Cancer Detection , 2012, PloS one.

[26]  J. Ajani Evolving chemotherapy for advanced gastric cancer. , 2005, The oncologist.

[27]  H. Larjava,et al.  Hannu Larjava Tissues Extracellular Matrix Molecules and their Receptors : An Overview with Special Emphasis on Periodontal , 1991 .

[28]  Ivan Stamenkovic,et al.  Functional structure and composition of the extracellular matrix , 2003, The Journal of pathology.

[29]  Shuichi Tsutsumi,et al.  Global gene expression analysis of gastric cancer by oligonucleotide microarrays. , 2002, Cancer research.

[30]  Jun Xia,et al.  Upregulated INHBA expression is associated with poor survival in gastric cancer , 2012, Medical Oncology.

[31]  Martin Kuiper,et al.  BiNGO: a Cytoscape plugin to assess overrepresentation of Gene Ontology categories in Biological Networks , 2005, Bioinform..

[32]  Satya vani Guttula,et al.  Analyzing Microarray Data of Alzheimer's Using Cluster Analysis to Identify the Biomarker Genes , 2012, International journal of Alzheimer's disease.

[33]  P. Kwok,et al.  Natural variation in four human collagen genes across an ethnically diverse population. , 2008, Genomics.

[34]  W. Fujibuchi,et al.  Alternative pre‐mRNA splicing in digestive tract malignancy , 2011, Cancer science.

[35]  Y. Mitani,et al.  Gene Expression Profile of Gastric Carcinoma , 2004, Cancer Research.

[36]  R. Peek,et al.  Helicobacter pylori: gastric cancer and beyond , 2010, Nature Reviews Cancer.

[37]  Nam-Soon Kim,et al.  Identification of gastric cancer-related genes using a cDNA microarray containing novel expressed sequence tags expressed in gastric cancer cells. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[38]  H. Yokozaki,et al.  Genetic and epigenetic changes in stomach cancer. , 2001, International review of cytology.

[39]  B. Mecham,et al.  Differential Expression of Extracellular Matrix-Mediated Pathways in Single-Suture Craniosynostosis , 2011, PloS one.

[40]  S. Taylor,et al.  Specificity of LIM Domain Interactions with Receptor Tyrosine Kinases* , 1996, The Journal of Biological Chemistry.

[41]  J. Massagué,et al.  Cancer Metastasis: Building a Framework , 2006, Cell.

[42]  I. Okazaki,et al.  Collagen biosynthesis in gastric cancer: Immunohistochemical analysis of prolyl 4‐hydroxylase , 1999, Journal of surgical oncology.

[43]  Gordon K. Smyth,et al.  limma: Linear Models for Microarray Data , 2005 .

[44]  Hirofumi Nakayama,et al.  Search for new biomarkers of gastric cancer through serial analysis of gene expression and its clinical implications , 2004, Cancer science.

[45]  D. Komura,et al.  The niche component periostin is produced by cancer-associated fibroblasts, supporting growth of gastric cancer through ERK activation. , 2014, The American journal of pathology.

[46]  J. Machado,et al.  Molecular Pathogenesis of Gastric Cancer , 2013, Helicobacter.

[47]  A. Barabasi,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[48]  Y. Fukushima,et al.  Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer , 1999, British Journal of Cancer.

[49]  Hirofumi Nakayama,et al.  Molecular-pathological prognostic factors of gastric cancer: a review , 2005, Gastric Cancer.

[50]  C. Mathers,et al.  Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 , 2010, International journal of cancer.