{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:55:51Z","timestamp":1753890951853,"version":"3.41.2"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background<\/jats:bold><jats:bold>:<\/jats:bold> Owing to complex molecular mechanisms in gastric cancer (GC) oncogenesis and progression, existing biomarkers and therapeutic targets could not significantly improve diagnosis and prognosis. This study aims to identify the key genes and signaling pathways related to GC oncogenesis and progression using bioinformatics and meta-analysis methods.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Eligible microarray datasets were downloaded and integrated using the meta-analysis method. According to the tumor stage, GC gene chips were classified into three groups. Thereafter, the three groups\u2019 differentially expressed genes (DEGs) were identified by comparing the gene data of the tumor groups with those of matched normal specimens. Enrichment analyses were conducted based on common DEGs among the three groups. Then protein\u2013protein interaction (PPI) networks were constructed to identify relevant hub genes and subnetworks. The effects of significant DEGs and hub genes were verified and explored in other datasets. In addition, the analysis of mutated genes was also conducted using gene data from The Cancer Genome Atlas database.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> After integration of six microarray datasets, 1,229 common DEGs consisting of 1,065 upregulated and 164 downregulated genes were identified. Alpha-2 collagen type I (COL1A2), tissue inhibitor matrix metalloproteinase 1 (TIMP1), thymus cell antigen 1 (THY1), and biglycan (BGN) were selected as significant DEGs throughout GC development. The low expression of ghrelin (GHRL) is associated with a high lymph node ratio (LNR) and poor survival outcomes. Thereafter, we constructed a PPI network of all identified DEGs and gained 39 subnetworks and the top 20 hub genes. Enrichment analyses were performed for common DEGs, the most related subnetwork, and the top 20 hub genes. We also selected 61 metabolic DEGs to construct PPI networks and acquired the relevant hub genes. Centrosomal protein 55 (CEP55) and POLR1A were identified as hub genes associated with survival outcomes.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The DEGs, hub genes, and enrichment analysis for GC with different stages were comprehensively investigated, which contribute to exploring the new biomarkers and therapeutic targets.<\/jats:p>","DOI":"10.3389\/fgene.2022.881948","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T05:33:50Z","timestamp":1658468030000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Common Core Genes Play Vital Roles in Gastric Cancer With Different Stages"],"prefix":"10.3389","volume":"13","author":[{"given":"Zhiyuan","family":"Yu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaiyu","family":"Tu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuzhong","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyu","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peiyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.6004\/jnccn.2016.0137","article-title":"Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology","volume":"14","author":"Ajani","year":"2016","journal-title":"J. Natl. Compr. Canc Netw."},{"key":"B2","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA a cancer J. Clin."},{"key":"B3","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1016\/j.yexcr.2005.12.015","article-title":"Borealin\/Dasra B Is a Cell Cycle-Regulated Chromosomal Passenger Protein and its Nuclear Accumulation Is Linked to Poor Prognosis for Human Gastric Cancer","volume":"312","author":"Chang","year":"2006","journal-title":"Exp. Cell. Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1273","DOI":"10.3748\/wjg.v11.i9.1273","article-title":"A Microarray-Based Gastric Carcinoma Prewarning System","volume":"11","author":"Cui","year":"2005","journal-title":"Wjg"},{"key":"B5","doi-asserted-by":"publisher","first-page":"205","DOI":"10.3390\/cells9010205","article-title":"The Reverse Warburg Effect Is Associated with Fbp2-dependent Hif1\u03b1 Regulation in Cancer Cells Stimulated by Fibroblasts","volume":"9","author":"Duda","year":"2020","journal-title":"Cells"},{"key":"B6","doi-asserted-by":"publisher","first-page":"881015","DOI":"10.3389\/fonc.2022.881015","article-title":"Identification by Bioinformatics Analysis of Potential Key Genes Related to the Progression and Prognosis of Gastric Cancer","volume":"12","author":"Gao","year":"2022","journal-title":"Front. Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"144859","DOI":"10.1016\/j.gene.2020.144859","article-title":"Mining Topoisomerase Isoforms in Gastric Cancer","volume":"754","author":"Hou","year":"2020","journal-title":"Gene"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1016\/j.molonc.2016.08.002","article-title":"Biglycan Stimulates VEGF Expression in Endothelial Cells by Activating the TLR Signaling Pathway","volume":"10","author":"Hu","year":"2016","journal-title":"Mol. Oncol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1515\/raon-2015-0047","article-title":"Association between Polymorphisms in Segregation Genes BUB1B and TTK and Gastric Cancer Risk","volume":"50","author":"Hudler","year":"2016","journal-title":"Radiology Oncol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"44","DOI":"10.3892\/ijo.2012.1687","article-title":"Expression of Pyruvate Dehydrogenase Kinase-1 in Gastric Cancer as a Potential Therapeutic Target","volume":"42","author":"Hur","year":"2013","journal-title":"Int. J. Oncol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1159\/000447303","article-title":"Overexpression of KIF11 in Gastric Cancer with Intestinal Mucin Phenotype","volume":"84","author":"Imai","year":"2017","journal-title":"Pathobiology"},{"key":"B12","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1002\/ags3.12438","article-title":"Essential Updates 2019\/2020: Perioperative and Surgical Management of Gastric Cancer","volume":"5","author":"Irino","year":"2021","journal-title":"Ann. Gastroenterol. Surg."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e0198347","DOI":"10.1371\/journal.pone.0198347","article-title":"Folate Receptor 1 (FOLR1) Targeted Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Gastric Cancer","volume":"13","author":"Kim","year":"2018","journal-title":"PloS one"},{"key":"B14","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.humpath.2018.10.029","article-title":"Spindle Assembly Checkpoint MAD2 and CDC20 Overexpressions and Cell-In-Cell Formation in Gastric Cancer and its Precursor Lesions","volume":"85","author":"Kim","year":"2019","journal-title":"Hum. Pathol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1016\/j.ccr.2008.05.005","article-title":"Tumor Cell Metabolism: Cancer's Achilles' Heel","volume":"13","author":"Kroemer","year":"2008","journal-title":"Cancer Cell."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.3390\/cancers12061418","article-title":"Pharmacogenomic Analysis Reveals CCNA2 as a Predictive Biomarker of Sensitivity to Polo-Like Kinase I Inhibitor in Gastric Cancer","volume":"12","author":"Lee","year":"2020","journal-title":"Cancers"},{"key":"B17","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1186\/1476-4598-12-110","article-title":"Decreased Fructose-1,6-Bisphosphatase-2 Expression Promotes Glycolysis and Growth in Gastric Cancer Cells","volume":"12","author":"Li","year":"2013","journal-title":"Mol. Cancer"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e13488","DOI":"10.7717\/peerj.13488","article-title":"Association of Multiple Tumor Markers with Newly Diagnosed Gastric Cancer Patients: a Retrospective Study","volume":"10","author":"Li","year":"2022","journal-title":"PeerJ"},{"key":"B19","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.bbcan.2017.02.002","article-title":"Ghrelin and Cancer Progression","volume":"1868","author":"Lin","year":"2017","journal-title":"Biochimica Biophysica Acta (BBA) - Rev. Cancer"},{"key":"B20","doi-asserted-by":"publisher","first-page":"122","DOI":"10.3892\/ijo.2020.5048","article-title":"Upregulated Expression of SAC3D1 Is Associated with Progression in Gastric Cancer","volume":"57","author":"Liu","year":"2020","journal-title":"Int. J. Oncol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"24402","DOI":"10.18632\/aging.203688","article-title":"miR-6745-TIMP1 axis Inhibits Cell Growth and Metastasis in Gastric Cancer","volume":"13","author":"Liu","year":"2021","journal-title":"Aging"},{"key":"B22","doi-asserted-by":"publisher","first-page":"144447","DOI":"10.1016\/j.gene.2020.144447","article-title":"Novel CpG-SNPs in the Gastric Acid Secretion Pathway GNAI3 and Susceptibility to Gastric Cancer","volume":"736","author":"Liu","year":"2020","journal-title":"Gene"},{"key":"B23","doi-asserted-by":"publisher","first-page":"S20","DOI":"10.21037\/jgo-20-232","article-title":"Review of Management and Treatment of Peritoneal Metastases from Gastric Cancer Origin","volume":"12","author":"Manzanedo","year":"2021","journal-title":"J. Gastrointest. Oncol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1166\/jbn.2015.2113","article-title":"Genetic Variation of BCL2 (Rs2279115), NEIL2 (Rs804270), LTA (Rs909253), PSCA (Rs2294008) and PLCE1 (Rs3765524, Rs10509670) Genes and Their Correlation to Gastric Cancer Risk Based on Universal Tagged Arrays and Fe3O4 Magnetic Nanoparticles","volume":"11","author":"Mou","year":"2015","journal-title":"J. Biomed. Nanotechnol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12935-020-01644-7","article-title":"LncRNA LIFR-AS1 Promotes Proliferation and Invasion of Gastric Cancer Cell via miR-29a-3p\/COL1A2 axis","volume":"21","author":"Pan","year":"2021","journal-title":"Cancer Cell. Int."},{"key":"B26","doi-asserted-by":"publisher","first-page":"693360","DOI":"10.3389\/fonc.2021.693360","article-title":"Identification of Key Circulating Exosomal microRNAs in Gastric Cancer","volume":"11","author":"Qian","year":"2021","journal-title":"Front. Oncol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"153303382110049","DOI":"10.1177\/15330338211004944","article-title":"LAMB1 Is Related to the T Stage and Indicates Poor Prognosis in Gastric Cancer","volume":"20","author":"Ran","year":"2021","journal-title":"Technol. Cancer Res. Treat."},{"key":"B28","doi-asserted-by":"publisher","first-page":"7093","DOI":"10.1016\/j.biomaterials.2012.06.053","article-title":"HER2 Monoclonal Antibody Conjugated RNase-A-Associated CdTe Quantum Dots for Targeted Imaging and Therapy of Gastric Cancer","volume":"33","author":"Ruan","year":"2012","journal-title":"Biomaterials"},{"key":"B29","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: a Software Environment for Integrated Models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"6205","DOI":"10.2147\/CMAR.S176147","article-title":"Upregulation of KIF20A Correlates with Poor Prognosis in Gastric Cancer","volume":"10","author":"Sheng","year":"2018","journal-title":"Cmar"},{"key":"B31","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1007\/s00104-021-01355-3","article-title":"Neoadjuvante und perioperative Therapie des Magenkarzinoms, aktuelle Studien und neue Biomarker","volume":"92","author":"Stocker","year":"2021","journal-title":"Chirurg"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1016\/j.biopha.2017.11.015","article-title":"LINC00152\/miR-139-5p Regulates Gastric Cancer Cell Aerobic Glycolysis by Targeting PRKAA1","volume":"97","author":"Sun","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B33","doi-asserted-by":"publisher","first-page":"4389","DOI":"10.1007\/s13277-013-1578-1","article-title":"CEP55 Contributes to Human Gastric Carcinoma by Regulating Cell Proliferation","volume":"35","author":"Tao","year":"2014","journal-title":"Tumor Biol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"6093","DOI":"10.2147\/OTT.S247393","article-title":"Differential Metabolic Alterations and Biomarkers between Gastric Cancer and Colorectal Cancer: A Systematic Review and Meta-Analysis","volume":"13","author":"Tian","year":"2020","journal-title":"Ott"},{"key":"B35","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s12957-016-1095-y","article-title":"TPX2 Expression Is Associated with Poor Survival in Gastric Cancer","volume":"15","author":"Tomii","year":"2017","journal-title":"World J. Surg. Onc"},{"key":"B36","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1093\/bioinformatics\/bty721","article-title":"ImaGEO: Integrative Gene Expression Meta-Analysis from GEO Database","volume":"35","author":"Toro-Dom\u00ednguez","year":"2019","journal-title":"Bioinforma. Oxf. Engl."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1080\/00365521.2019.1663446","article-title":"Gastric Cancer and Gastrin: on the Interaction of Helicobacter pylori Gastritis and Acid Inhibitory Induced Hypergastrinemia","volume":"54","author":"Waldum","year":"2019","journal-title":"Scand. J. gastroenterology"},{"key":"B38","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s40880-019-0349-9","article-title":"The Chinese Society of Clinical Oncology (CSCO): Clinical Guidelines for the Diagnosis and Treatment of Gastric Cancer","volume":"39","author":"Wang","year":"2019","journal-title":"Cancer Commun."},{"key":"B39","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/1477-3155-9-23","article-title":"BRCAA1 Monoclonal Antibody Conjugated Fluorescent Magnetic Nanoparticles for In Vivo Targeted Magnetofluorescent Imaging of Gastric Cancer","volume":"9","author":"Wang","year":"2011","journal-title":"J. Nanobiotechnol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"BSR20202564","DOI":"10.1042\/BSR20202564","article-title":"Bioinformatics Analysis Identifies COL1A1, THBS2 and SPP1 as Potential Predictors of Patient Prognosis and Immunotherapy Response in Gastric Cancer","volume":"41","author":"Wang","year":"2021","journal-title":"Biosci. Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"BSR20181434","DOI":"10.1042\/BSR20181434","article-title":"MicroRNA-140-5p Inhibits Cell Proliferation, Migration and Promotes Cell Apoptosis in Gastric Cancer through the Negative Regulation of THY1-Mediated Notch Signaling","volume":"39","author":"Wu","year":"2019","journal-title":"Biosci. Rep."},{"key":"B42","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1186\/s11671-015-1153-3","article-title":"A Novel Electrochemical Microfluidic Chip Combined with Multiple Biomarkers for Early Diagnosis of Gastric Cancer","volume":"10","author":"Xie","year":"2015","journal-title":"Nanoscale Res. Lett."},{"key":"B43","doi-asserted-by":"publisher","first-page":"15412","DOI":"10.1038\/s41598-021-94291-5","article-title":"Combined Bioinformatics Technology to Explore Pivot Genes and Related Clinical Prognosis in the Development of Gastric Cancer","volume":"11","author":"Xu","year":"2021","journal-title":"Sci. Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"14392","DOI":"10.1111\/jcmm.16060","article-title":"SLC1A3 Promotes Gastric Cancer Progression via the PI3K\/AKT Signalling Pathway","volume":"24","author":"Xu","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"B45","doi-asserted-by":"publisher","first-page":"792","DOI":"10.7150\/ijms.47339","article-title":"Integrated Bioinformatics Analysis for Differentially Expressed Genes and Signaling Pathways Identification in Gastric Cancer","volume":"18","author":"Yang","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"733","DOI":"10.7150\/thno.10305","article-title":"Circulating MiR-16-5p and MiR-19b-3p as Two Novel Potential Biomarkers to Indicate Progression of Gastric Cancer","volume":"5","author":"Zhang","year":"2015","journal-title":"Theranostics"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/8831466","article-title":"Coexpression of Matrix Metalloproteinase-7 and Tissue Inhibitor of Metalloproteinase-1 as a Prognostic Biomarker in Gastric Cancer","volume":"2020","author":"Zhang","year":"2020","journal-title":"Dis. markers"},{"key":"B48","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s12957-022-02616-z","article-title":"Accuracy Evaluation of Combining Gastroscopy, Multi-Slice Spiral CT, Her-2, and Tumor Markers in Gastric Cancer Staging Diagnosis","volume":"20","author":"Zhao","year":"2022","journal-title":"World J. Surg. Onc"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.881948\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T05:33:52Z","timestamp":1658468032000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.881948\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":48,"alternative-id":["10.3389\/fgene.2022.881948"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.881948","relation":{},"ISSN":["1664-8021"],"issn-type":[{"type":"electronic","value":"1664-8021"}],"subject":[],"published":{"date-parts":[[2022,7,22]]},"article-number":"881948"}}