title: Unraveling Molecular Differences of Gastric Cancer by Label-Free Quantitative Proteomics Analysis.
abstract: Gastric cancer (GC) has significant morbidity and mortality worldwide and especially in China. Its molecular pathogenesis has not been thoroughly elaborated. The acknowledged biomarkers for diagnosis, prognosis, recurrence monitoring and treatment are lacking. Proteins from matched pairs of human GC and adjacent tissues were analyzed by a coupled label-free Mass Spectrometry (MS) approach, followed by functional annotation with software analysis. Nano-LC-MS/MS, quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry were used to validate dysregulated proteins. One hundred forty-six dysregulated proteins with more than twofold expressions were quantified, 22 of which were first reported to be relevant with GC. Most of them were involved in cancers and gastrointestinal disease. The expression of a panel of four upregulated nucleic acid binding proteins, heterogeneous nuclear ribonucleoprotein hnRNPA2B1, hnRNPD, hnRNPL and Y-box binding protein 1 (YBX-1) were validated by Nano-LC-MS/MS, qRT-PCR, western blot and immunohistochemistry assays in ten GC patients' tissues. They were located in the keynotes of a predicted interaction network and might play important roles in abnormal cell growth. The label-free quantitative proteomic approach provides a deeper understanding and novel insight into GC-related molecular changes and possible mechanisms. It also provides some potential biomarkers for clinical diagnosis.
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. rarfen@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. maomao_snnu@163.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. weihuawang@email.arizona.edu.
authors.forename: Weihua
authors.initials: W
authors.lastname: Wang
authors.affiliation: The Cancer Research Center, School of Medicine, Shandong University, Jinan 250012, China. jingruirui223@163.com.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Jing
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. wangwei_fmmu@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: The Cancer Research Center, School of Medicine, Shandong University, Jinan 250012, China. 15554139558@163.com.
authors.forename: Fengqin
authors.initials: F
authors.lastname: Wang
authors.affiliation: Departments of Surgery and Urology, Boston Veterans Affairs Healthcare System, Boston University School of Medicine, Boston, MA 02130, USA. kazadzoi@bu.edu.
authors.forename: Kazem M
authors.initials: KM
authors.lastname: Azadzoi
authors.affiliation: The Cancer Research Center, School of Medicine, Shandong University, Jinan 250012, China. jyang@bu.edu.|Departments of Surgery and Urology, Boston Veterans Affairs Healthcare System, Boston University School of Medicine, Boston, MA 02130, USA. jyang@bu.edu.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cancer Biology, Department of Pharmacogenomics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China. yanzhen@fmmu.edu.cn.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics* / Q000378:metabolism; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D011379:Prognosis; D025941:Protein Interaction Mapping; D040901:Proteomics / Q000379:methods; D012008:Recurrence; D012261:Ribonucleoproteins / Q000235:genetics*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D059016:Tumor Microenvironment / Q000235:genetics; D051840:Y-Box-Binding Protein 1 / Q000235:genetics*; D034664:Heterogeneous-Nuclear Ribonucleoprotein L
chemical_list: D014408:Biomarkers, Tumor; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D012261:Ribonucleoproteins; D051840:Y-Box-Binding Protein 1; C400563:HNRNPL protein, human; D034664:Heterogeneous-Nuclear Ribonucleoprotein L; C070856:YBX1 protein, human; C439768:hnRNP A2
keywords: LC-MS/MS; Label-free quantitative proteomics; Y-box binding protein 1; gastric cancer; heterogeneous nuclear ribonucleoprotein