title: Protein-protein interaction analysis of distinct molecular pathways in two subtypes of colorectal carcinoma.
abstract: The aim of this study was to identify the molecular events that distinguish serrated colorectal carcinoma (SCRC) from conventional colorectal carcinoma (CCRC) through differential gene expression, pathway and protein-protein interaction (PPI) network analysis. The GSE4045 and GSE8671 microarray datasets were downloaded from the Gene Expression Omnibus database. We identified the genes that are differentially expressed between SCRC and normal colon tissues, CCRC and healthy tissues, and between SCRC and CCRC using Student's t-tests and Benjamini‑Hochberg (BH) multiple testing corrections. The differentially expressed genes (DEGs) were then mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and their enrichment for specific pathways was investigated using the Database for Annotation, Visualization and Integrated Discovery (DAVID) tool with a significance threshold of 0.1. Analysis of the potential interactions between the protein products of 220 DEGs (between CCRC and SCRC) was performed by constructing a PPI network using data from the high performance RDF database (P<0.1). The interaction between pathways was also analyzed in CCRC based on the PPI network. Our study identified thousands of genes differentially expressed in SCRC and CCRC compared to healthy tissues. The DEGs in SCRC and CCRC were enriched in cell cycle, DNA replication, and base excision repair pathways. The proteasome pathway was significantly enriched in SCRC but not in CCRC after BH adjustment. The PPI network showed that tumour necrosis factor receptor-associated factor 6 (TRAF6) and atrophin 1 (ATN1) were the most central genes in the network, with respective degrees of node predicted at 90 and 88. In conclusion, the preoteasome pathway was shown to be specifically enriched in SCRC. Furthermore, TRAF6 and ATN1 may be promising biomarkers for the distinction between serrated and conventional CRC.
authors.affiliation: Department of Pathology, Central Hospital of Shanghai Zhabei District, Shanghai 200070, P.R. China.
authors.forename: Hanzhang
authors.initials: H
authors.lastname: Chen
authors.affiliation: The Operating Room, Central Hospital of Shanghai Zhabei District, Shanghai 200070, P.R. China.
authors.forename: Yunzhen
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai Tongji Hospital, Shanghai 200065, P.R. China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai Tongji Hospital, Shanghai 200065, P.R. China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: Urology Surgery, The First People's Hospital of Jingzhou, Hubei 434000, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai Tongji Hospital, Shanghai 200065, P.R. China.
authors.forename: Pan
authors.initials: P
authors.lastname: Gu
authors.affiliation: Hematology Department, University Medical Center of Princeton, Plainsboro, NJ 08536, USA.
authors.forename: Xia
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai Tongji Hospital, Shanghai 200065, P.R. China.
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai Tongji Hospital, Shanghai 200065, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai Tongji Hospital, Shanghai 200065, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai Tongji Hospital, Shanghai 200065, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai Tongji Hospital, Shanghai 200065, P.R. China.
authors.forename: Weizhe
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Pathology, University Medical Center of Princeton, Plainsboro, NJ 08536, USA.
authors.forename: Lanjing
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai Tongji Hospital, Shanghai 200065, P.R. China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Yi
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics; D060066:Protein Interaction Maps / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics
chemical_list: D009419:Nerve Tissue Proteins; D048029:TNF Receptor-Associated Factor 6; C095278:atrophin-1; D046988:Proteasome Endopeptidase Complex