title: Integrative topological analysis of mass spectrometry data reveals molecular features with clinical relevance in esophageal squamous cell carcinoma.
abstract: Combining MS-based proteomic data with network and topological features of such network would identify more clinically relevant molecules and meaningfully expand the repertoire of proteins derived from MS analysis. The integrative topological indexes representing 95.96% information of seven individual topological measures of node proteins were calculated within a protein-protein interaction (PPI) network, built using 244 differentially expressed proteins (DEPs) identified by iTRAQ 2D-LC-MS/MS. Compared with DEPs, differentially expressed genes (DEGs) and comprehensive features (CFs), structurally dominant nodes (SDNs) based on integrative topological index distribution produced comparable classification performance in three different clinical settings using five independent gene expression data sets. The signature molecules of SDN-based classifier for distinction of early from late clinical TNM stages were enriched in biological traits of protein synthesis, intracellular localization and ribosome biogenesis, which suggests that ribosome biogenesis represents a promising therapeutic target for treating ESCC. In addition, ITGB1 expression selected exclusively by integrative topological measures correlated with clinical stages and prognosis, which was further validated with two independent cohorts of ESCC samples. Thus the integrative topological analysis of PPI networks proposed in this study provides an alternative approach to identify potential biomarkers and therapeutic targets from MS/MS data with functional insights in ESCC.
authors.affiliation: Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, P. R. China, 471003.
authors.forename: She-Gan
authors.initials: SG
authors.lastname: Gao
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Henan International United Laboratory of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Henan University School of Medicine, Kaifeng 475004, P.R. China.
authors.forename: Rui-Min
authors.initials: RM
authors.lastname: Liu
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Henan International United Laboratory of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Henan University School of Medicine, Kaifeng 475004, P.R. China.
authors.forename: Yun-Gang
authors.initials: YG
authors.lastname: Zhao
authors.affiliation: School of Mathematics and Statistics, Henan University, Kaifeng, China, Henan 475004, P. R. China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.affiliation: School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Ward
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Henan International United Laboratory of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Henan University School of Medicine, Kaifeng 475004, P.R. China.
authors.forename: Guang-Chao
authors.initials: GC
authors.lastname: Wang
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Henan International United Laboratory of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Henan University School of Medicine, Kaifeng 475004, P.R. China.
authors.forename: Xiang-Qian
authors.initials: XQ
authors.lastname: Guo
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Henan International United Laboratory of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Henan University School of Medicine, Kaifeng 475004, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Gu
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Henan International United Laboratory of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Henan University School of Medicine, Kaifeng 475004, P.R. China.
authors.forename: Wan-Bin
authors.initials: WB
authors.lastname: Niu
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Henan International United Laboratory of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Henan University School of Medicine, Kaifeng 475004, P.R. China.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.affiliation: School of Cancer Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
authors.forename: Ashley
authors.initials: A
authors.lastname: Martin
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Henan International United Laboratory of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Henan University School of Medicine, Kaifeng 475004, P.R. China.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Guo
authors.affiliation: Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, P. R. China, 471003.
authors.forename: Xiao-Shan
authors.initials: XS
authors.lastname: Feng
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Henan International United Laboratory of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Henan University School of Medicine, Kaifeng 475004, P.R. China.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Qi
authors.affiliation: Henan Key Laboratory of Engineering Antibody Medicine, Henan International United Laboratory of Antibody Medicine, Key Laboratory of Cellular and Molecular Immunology, Henan University School of Medicine, Kaifeng 475004, P.R. China.
authors.forename: Yuan-Fang
authors.initials: YF
authors.lastname: Ma
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D058990:Molecular Targeted Therapy; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D060066:Protein Interaction Maps / Q000235:genetics*; D040901:Proteomics; D012270:Ribosomes / Q000235:genetics; D053719:Tandem Mass Spectrometry
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C108257:ITGB1BP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins