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Tytuł:
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Primary tumor xenografts of human lung adeno and squamous cell carcinoma express distinct proteomic signatures.
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Autorzy:
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Wei Y; Program in Molecular Structure and Function, Hospital For Sick Children, University Health Network, Ontario Cancer Institute/Princess Margaret Hospital, Toronto, Canada.
Tong J
Taylor P
Strumpf D
Ignatchenko V
Pham NA
Yanagawa N
Liu G
Jurisica I
Shepherd FA
Tsao MS
Kislinger T
Moran MF
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Źródło:
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Journal of proteome research [J Proteome Res] 2011 Jan 07; Vol. 10 (1), pp. 161-74. Date of Electronic Publication: 2010 Sep 24.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Original Publication: Washington, D.C. : American Chemical Society, c2002-
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MeSH Terms:
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Neoplasm Transplantation*
Adenocarcinoma/*metabolism
Carcinoma, Non-Small-Cell Lung/*metabolism
Carcinoma, Squamous Cell/*metabolism
Proteome/*metabolism
Animals ; Blotting, Western ; Chromatography, Liquid ; Cluster Analysis ; ErbB Receptors/metabolism ; Humans ; Immunohistochemistry ; Keratin-7/metabolism ; Keratins/metabolism ; Mice ; Mice, Inbred NOD ; Proteome/analysis ; Reproducibility of Results ; Statistics, Nonparametric ; Tandem Mass Spectrometry ; Transplantation, Heterologous
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Grant Information:
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STP 53912 Canada Canadian Institutes of Health Research
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Substance Nomenclature:
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0 (KRT7 protein, human)
0 (Keratin-7)
0 (Proteome)
68238-35-7 (Keratins)
EC 2.7.10.1 (ErbB Receptors)
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Entry Date(s):
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Date Created: 20100907 Date Completed: 20110516 Latest Revision: 20181201
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Update Code:
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20240104
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DOI:
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10.1021/pr100491e
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PMID:
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20815376
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Nonsmall cell lung carcinoma (NSCLC) accounts for 80% of lung cancers. The most prevalent subtypes of NSCLC are adenocarcinoma (ADC) and squamous cell carcinoma (SCC), which combined account for approximately 90%. Ten resected NSCLC patient tumors (5 ADC and 5 SCC) were directly introduced into severely immune deficient (NOD-SCID) mice, and the resulting xenograft tumors were analyzed by standard histology and immunohistochemistry (IHC) and by proteomics profiling. Mass spectrometry (MS) methods involving 1- and 2-dimensional LC-MS/MS, and multiplexed selective reaction monitoring (SRM, or MRM), were applied to identify and quantify the xenograft proteomes. Hierarchical clustering of protein profiles distinguished between the ADC and SCC subtypes. The differential expression of 178 proteins, including a comprehensive panel of intermediate filament keratin proteins, was found to constitute a distinctive proteomic signature associated with the NSCLC subtypes. Epidermal growth factor receptor (EGFR) was expressed in ADC and SCC xenografts, and EGFR network activation was assessed by phosphotyrosine profiling by Western blot analysis and SRM measurement of EGFR levels, and mutation analysis. A multiplexed SRM/MRM method provided relative quantification of several keratin proteins, EGFR and plakophilin-1 in single LC-MS/MS runs. The protein quantifications by SRM and MS/MS spectral counting were associated with superior dynamic range and reproducibility but were otherwise consistent with orthogonal methods including IHC and Western immuno blotting. These findings illustrate the potential to develop a comprehensive MS-based platform in oncologic pathology for better classification and potentially treatment of NSCLC patients.