کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8949170 | 1666279 | 2018 | 76 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Serum proteome mapping of EGF transgenic mice reveal mechanistic biomarkers of lung cancer precursor lesions with clinical significance for human adenocarcinomas
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کلمات کلیدی
EGFRapoA1AAHPLGA2MTTRAATAPOC3RTKapoMAPPGSNAPOA4IEF2-DEERKSurfactant protein-CGPX3MUPtransthyretinEGFSP-Ccolloidal coomassie blueCCBMALDI-TOFc-Myc - c-mycc-Raf - C-RafIPG - GPAimmobilized pH gradient - gradient pH immobilizedBAC - LACMAPK - MAPKα-1-antitrypsin - α-1-آنتی تیپسینα-2-Macroglobulin - α-2-ماکروگلوبولینAdenocarcinoma - آدنوکارسینوماApoH - آپوApoe - آپوApolipoprotein A-I - آپولیپوپروتئین A-IApolipoprotein A-IV - آپولیپوپروتئین A-IVApolipoprotein C-III - آپولیپوپروتئین C-IIIapolipoprotein E - آپولیپوپروتئین Eapolipoprotein H - آپولیپوپروتئین HApolipoprotein M - آپولیپوپروتئین مAraf - بزرخisoelectric focusing - تمرکز ذره ای الکتریکیcomputed tomography - توموگرافی کامپیوتری یا سی تی اسکن یا مقطعنگاری رایانهایSerum amyloid P component - جزء آمیلوئید P سرمNSCLC - سرطان ریوی غیر سلول کوچکSAP - شیرهepidermal growth factor - عامل رشد اپیدرمیmatrix-assisted laser desorption/ionization-time of flight - مدت زمان جذب / زمان یونیزاسیون لیزر ماتریس کمک می کندAtypical adenomatous hyperplasia - هیپرپلازی آدنوماتوز غیرطبیعیMajor urinary protein - پروتئین عمده ادرارAcute phase protein - پروتئین فاز حادVitamin D binding protein - پروتئین متصل به ویتامین Dmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenPlasminogen - پلاسمینوژنGelsolin - ژلزولینnon-small cell lung carcinoma - کارسینوم ریه سلول غیر سلولیextracellular signal-regulated kinase - کیناز تنظیم شده سیگنال خارج سلولیGlutathione peroxidase 3 - گلوتاتیون پراکسیداز 3Receptor Tyrosine Kinase - گیرنده تیروزین کینازEpidermal growth factor receptor - گیرنده فاکتور رشد اپیدرمال
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
Atypical adenomatous hyperplasia (AAH) of the lung is a pre-invasive lesion (PL) with high risk of progression to lung cancer (LC). However, the pathways involved are uncertain. We searched for novel mechanistic biomarkers of AAH in an EGF transgenic disease model of lung cancer. Disease regulated proteins were validated by Western immunoblotting and immunohistochemistry (IHC) of control and morphologically altered respiratory epithelium. Translational work involved clinical resection material. Collectively, 68 unique serum proteins were identified by 2DE-MALDI-TOF mass spectrometry and 13 reached statistical significance (pâ¯<â¯0.05). EGF, amphiregulin and the EGFR endosomal sorting protein VPS28 were induced up to 5-fold while IHC confirmed strong induction of these proteins. Furthermore, ApoA1, α-2-macroglobulin, and vitamin-D binding protein were nearly 6- and 2-fold upregulated in AAH; however, ApoA1 was oppositely regulated in LC to evidence disease stage dependent regulation of this tumour suppressor. Conversely, plasminogen and transthyretin were highly significantly repressed by 3- and 20-fold. IHC confirmed induced ApoA1, Fetuin-B and transthyretin expression to influence calcification, inflammation and tumour-infiltrating macrophages. Moreover, serum ApoA4, ApoH and ApoM were 2-, 2- and 6-fold repressed; however tissue ApoM and sphingosine-1-phosphate receptor expression was markedly induced to suggest a critical role of sphingosine-1-phosphate signalling in PL and malignant transformation. Finally, a comparison of three different LC models revealed common and unique serum biomarkers mechanistically linked to EGFR, cMyc and cRaf signalling. Their validation by IHC on clinical resection material established relevance for distinct human lung pathologies. In conclusion, we identified mechanistic biomarker candidates recommended for in-depth clinical evaluation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1864, Issue 10, October 2018, Pages 3122-3144
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1864, Issue 10, October 2018, Pages 3122-3144
نویسندگان
Jürgen Borlak, Florian Länger, Bijon Chatterji,