title: Proteomic analysis of solid pseudopapillary tumor of the pancreas reveals dysfunction of the endoplasmic reticulum protein processing pathway.
abstract: Solid pseudopapillary tumor of the pancreas (SPTP) is a low-grade malignant tumor with a favorable prognosis after surgery. Many previous studies have focused on clinical features or pathological biomarkers of the disease, but a better understanding of the molecular mechanisms underlying SPTP may help guide future therapeutic strategies. Here, we used isobaric tags for relative and absolute quantitation (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify differentially expressed proteins in SPTP specimens. A total of 1171 proteins with a threshold of a 1.5-fold change and a p value ≤ 0.05 between SPTP tissue and matched normal pancreas tissue were identified for bioinformatics analysis. Mass spectrometry results were then further confirmed by assessing six representative proteins (ACADL, EPHX2, MSI2, DKK4, JUP, and DAD1) in individual specimens with immunohistochemistry. Upon mapping of the differentially expressed proteins to the Kyoto Encyclopedia of Genes and Genomes pathways database, we found several new cell-adhesion molecules that could be used as pathologic biomarkers. Furthermore, we observed that many endoplasmic reticulum-associated proteins were altered, suggesting that endoplasmic reticulum stress may play an important role in SPTP tumorigenesis. Seven proteins (ERO1LB, TRIM1, GRP94, BIP, SEC61B, P4HB, and PDIA4) in this pathway were further validated by immunohistochemistry, and six of them (except SEC61B) coincided to the LC-MS/MS results. This first comprehensive analysis of the SPTP proteome confirms proteins that have been implicated in earlier reports and reveals novel candidates and pathways that could be investigated further for clinical applications.
authors.affiliation: From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China;
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: §Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China; haochendr@126.com chhpeng@188.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.affiliation: §Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Xie
authors.affiliation: From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China;
authors.forename: Minmin
authors.initials: M
authors.lastname: Shi
authors.affiliation: From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China;
authors.forename: Baiyong
authors.initials: B
authors.lastname: Shen
authors.affiliation: From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China;
authors.forename: Xiaxing
authors.initials: X
authors.lastname: Deng
authors.affiliation: From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China;
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China;
authors.forename: Xi
authors.initials: X
authors.lastname: Zhan
authors.affiliation: From the ‡Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China; haochendr@126.com chhpeng@188.com.
authors.forename: Chenghong
authors.initials: C
authors.lastname: Peng
mesh_terms: D000231:Adenocarcinoma, Papillary / Q000378:metabolism* / Q000473:pathology*; D002853:Chromatography, Liquid / Q000379:methods; D059865:Endoplasmic Reticulum Stress; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020543:Proteome / Q000302:isolation & purification*; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction
chemical_list: D020543:Proteome