Hao Li1, Jing-Wei Liu1, Shuang Liu1, Yuan Yuan2, Li-Ping Sun3. 1. Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, 110001, Liaoning, China. 2. Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, 110001, Liaoning, China. yuanyuan@cmu.edu.cn. 3. Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang, 110001, Liaoning, China. lpsun@cmu.edu.cn.
Abstract
BACKGROUND AND AIMS: The aim of the study was to identify methylated-differentially expressed genes (MDEGs) in gastric cancer and investigate their potential pathways. METHODS: Expression profiling (GSE13911 and GSE29272) and methylation profiling (GSE25869 and GSE30601) data were obtained from GEO DataSets. Differentially expressed genes and differentially methylated genes were identified using GEO2R. Gene ontology and pathway enrichment analyses were performed for the MDEGs. Protein-protein interaction (PPI) networks were established by STRING and Cytoscape. Analysis of modules in the PPI networks was performed using MCODE. Further, the hub genes derived from the PPI networks were verified by The Cancer Genome Atlas (TCGA) database and human tissues, with methylation-specific PCR for genes methylation and real-time qPCR for genes expression. RESULTS: A total of 445 genes were identified as hypermethylated, lowly expressed genes (Hyper-LGs), which were enriched in the regulation of system process and channel activity. A total of 129 genes were identified as hypomethylated, highly expressed genes (Hypo-HGs), which were involved in cell adhesion, cell proliferation, and protein binding. Pathway analysis showed that Hyper-LGs were associated with neuroactive ligand-receptor interaction and calcium signaling pathway, while Hypo-HGs were enriched in pathways in cancer. In the PPI networks, after verification by TCGA analysis and human tissue detection, CASR, CXCL12, and SST were identified as significantly different hub genes. CONCLUSIONS: MDEG analysis helps to understand the epigenetic regulation mechanisms involved in the development and progression of gastric cancer. The hub genes have predictive and prognostic value as methylation-based biomarkers for the precise diagnosis and treatment of gastric cancer.
BACKGROUND AND AIMS: The aim of the study was to identify methylated-differentially expressed genes (MDEGs) in gastric cancer and investigate their potential pathways. METHODS: Expression profiling (GSE13911 and GSE29272) and methylation profiling (GSE25869 and GSE30601) data were obtained from GEO DataSets. Differentially expressed genes and differentially methylated genes were identified using GEO2R. Gene ontology and pathway enrichment analyses were performed for the MDEGs. Protein-protein interaction (PPI) networks were established by STRING and Cytoscape. Analysis of modules in the PPI networks was performed using MCODE. Further, the hub genes derived from the PPI networks were verified by The Cancer Genome Atlas (TCGA) database and human tissues, with methylation-specific PCR for genes methylation and real-time qPCR for genes expression. RESULTS: A total of 445 genes were identified as hypermethylated, lowly expressed genes (Hyper-LGs), which were enriched in the regulation of system process and channel activity. A total of 129 genes were identified as hypomethylated, highly expressed genes (Hypo-HGs), which were involved in cell adhesion, cell proliferation, and protein binding. Pathway analysis showed that Hyper-LGs were associated with neuroactive ligand-receptor interaction and calcium signaling pathway, while Hypo-HGs were enriched in pathways in cancer. In the PPI networks, after verification by TCGA analysis and human tissue detection, CASR, CXCL12, and SST were identified as significantly different hub genes. CONCLUSIONS: MDEG analysis helps to understand the epigenetic regulation mechanisms involved in the development and progression of gastric cancer. The hub genes have predictive and prognostic value as methylation-based biomarkers for the precise diagnosis and treatment of gastric cancer.
Authors: Balázs Győrffy; Giulia Bottai; Thomas Fleischer; Gyöngyi Munkácsy; Jan Budczies; Laura Paladini; Anne-Lise Børresen-Dale; Vessela N Kristensen; Libero Santarpia Journal: Int J Cancer Date: 2015-07-30 Impact factor: 7.396
Authors: C A Eads; R V Lord; S K Kurumboor; K Wickramasinghe; M L Skinner; T I Long; J H Peters; T R DeMeester; K D Danenberg; P V Danenberg; P W Laird; K A Skinner Journal: Cancer Res Date: 2000-09-15 Impact factor: 12.701
Authors: Florian Eckhardt; Joern Lewin; Rene Cortese; Vardhman K Rakyan; John Attwood; Matthias Burger; John Burton; Tony V Cox; Rob Davies; Thomas A Down; Carolina Haefliger; Roger Horton; Kevin Howe; David K Jackson; Jan Kunde; Christoph Koenig; Jennifer Liddle; David Niblett; Thomas Otto; Roger Pettett; Stefanie Seemann; Christian Thompson; Tony West; Jane Rogers; Alex Olek; Kurt Berlin; Stephan Beck Journal: Nat Genet Date: 2006-10-29 Impact factor: 38.330