PMID- 31848941 OWN - NLM STAT- MEDLINE DCOM- 20210406 LR - 20211204 IS - 1532-2807 (Electronic) IS - 1219-4956 (Linking) VI - 26 IP - 3 DP - 2020 Jul TI - Identification of Key Genes and Signaling Pathways Associated with the Progression of Gastric Cancer. PG - 1903-1919 LID - 10.1007/s12253-019-00781-3 [doi] AB - Genomic features have been gradually regarded as part of the fundamentals to the clinical diagnosis and treatment for gastric cancer. However, the molecular alterations taking place during the progression of gastric cancer remain unclear. Therefore, identification of potential key genes and pathways in the gastric cancer progression is crucial to clinical practices. The gene expression profile, GSE103236, was retrieved for the identification of the differentially expressed genes (DEGs), followed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichments, gene set enrichment analysis (GSEA) and the protein-protein interaction (PPI) networks. Multiple bioinformatics platforms were employed for expression and prognostic analysis. Fresh frozen gastric cancer tissues were used for external validation. A total of 161 DEGs were identified from GSE103236. The PPI network-derived hub genes included collagen type I alpha 1 chain (COL1A1), tissue inhibitor of the metalloproteinases (TIMP1), Secreted Phosphoprotein 1 (SPP1), somatostatin (SST), neuropeptide Y (NPY), biglycan (BGN), matrix metallopeptidase 3 (MMP3), apolipoprotein E (APOE), ATPase H+/K+ transporting alpha subunit (ATP4A), lysyl oxidase (LOX). SPP1 (log rank p = 0.0048, HR = 1.39 [1.1-1.75]) and MMP3 (log rank p < 0.0001, HR = 1.77 [1.44-2.19]) were significantly associated with poor overall survival. Stage-specifically, both COL1A1 and BGN were correlated with significant in stage III and IV gastric cancer cases. LOX showed significant correlation with prognosis in stage I and stage II gastric cancer cases. Furthermore, cg00583003 of SPP1 and cg16466334 of MMP3 exhibited highly methylation level and significant prognostic values (SPP1: HR = 1.625, p = 0.013; MMP3: HR = 0.647, p = 0.011). Hub genes signature displayed a favorable prognostic value (p value = 5.227e-05). APOE demonstrated the highest correlation with CD8(+) T cells, neutrophils, and dendritic cells whereas BGN had the highest correlation with macrophages. This study systematically explored the key genes and pathways involved in PGC and AGC, providing insights into therapeutic individualized management. FAU - Yu, Chaoran AU - Yu C AD - Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China. chaoran_yu@sjtu.edu.cn. FAU - Chen, Jie AU - Chen J AD - Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China. AD - Department of Nursing, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200025, People's Republic of China. FAU - Ma, Junjun AU - Ma J AD - Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China. FAU - Zang, Lu AU - Zang L AD - Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China. FAU - Dong, Feng AU - Dong F AD - Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China. FAU - Sun, Jing AU - Sun J AD - Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China. FAU - Zheng, Minhua AU - Zheng M AD - Department of Gastrointestinal Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China. LA - eng GR - 81402423/National Natural Science Foundation of China/ GR - 81572818/National Natural Science Foundation of China/ GR - 81871984/National Natural Science Foundation of China/ GR - 2017YQ062/Shanghai Municipal Population and Family Planning Commission (CN)/ GR - 18695841400/Shanghai Science and Technology Committee/ PT - Journal Article DEP - 20191217 PL - Switzerland TA - Pathol Oncol Res JT - Pathology oncology research : POR JID - 9706087 RN - 0 (Biomarkers, Tumor) RN - 0 (COL1A1 protein, human) RN - 0 (Collagen Type I, alpha 1 Chain) SB - IM MH - Biomarkers, Tumor/*genetics/*metabolism MH - Collagen Type I, alpha 1 Chain MH - Disease Progression MH - Humans MH - Prognosis MH - Signal Transduction/physiology MH - Stomach Neoplasms/*genetics/*pathology MH - Transcriptome OTO - NOTNLM OT - Differentially expressed genes OT - Gastric cancer OT - Gene ontology OT - Gene set enrichment analysis OT - KEGG pathway OT - Protein-protein interaction network EDAT- 2019/12/19 06:00 MHDA- 2021/04/07 06:00 CRDT- 2019/12/19 06:00 PHST- 2019/08/03 00:00 [received] PHST- 2019/11/19 00:00 [accepted] PHST- 2019/12/19 06:00 [pubmed] PHST- 2021/04/07 06:00 [medline] PHST- 2019/12/19 06:00 [entrez] AID - 10.1007/s12253-019-00781-3 [pii] AID - 10.1007/s12253-019-00781-3 [doi] PST - ppublish SO - Pathol Oncol Res. 2020 Jul;26(3):1903-1919. doi: 10.1007/s12253-019-00781-3. Epub 2019 Dec 17.