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HPB (Oxford) ; 20(6): 563-572, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29352660

RESUMEN

BACKGROUND: Poor prognosis of pancreatic cancer (PanCa) is associated with lack of an effective early diagnostic biomarker. This study elucidates significance of MUC13, as a diagnostic/prognostic marker of PanCa. METHODS: MUC13 was assessed in tissues using our in-house generated anti-MUC13 mouse monoclonal antibody and analyzed for clinical correlation by immunohistochemistry, immunoblotting, RT-PCR, computational and submicron scale mass-density fluctuation analyses, ROC and Kaplan Meir curve analyses. RESULTS: MUC13 expression was detected in 100% pancreatic intraepithelial neoplasia (PanIN) lesions (Mean composite score: MCS = 5.8; AUC >0.8, P < 0.0001), 94.6% of pancreatic ductal adenocarcinoma (PDAC) samples (MCS = 9.7, P < 0.0001) as compared to low expression in tumor adjacent tissues (MCS = 4, P < 0.001) along with faint or no expression in normal pancreatic tissues (MCS = 0.8; AUC >0.8; P < 0.0001). Nuclear MUC13 expression positively correlated with nodal metastasis (P < 0.05), invasion of cancer to peripheral tissues (P < 0.5) and poor patient survival (P < 0.05; prognostic AUC = 0.9). Submicron scale mass density and artificial intelligence based algorithm analyses also elucidated association of MUC13 with greater morphological disorder (P < 0.001) and nuclear MUC13 as strong predictor for cancer aggressiveness and poor patient survival. CONCLUSION: This study provides significant information regarding MUC13 expression/subcellular localization in PanCa samples and supporting the use anti-MUC13 MAb for the development of PanCa diagnostic/prognostic test.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma in Situ/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Mucinas/metabolismo , Neoplasias Pancreáticas/metabolismo , Biomarcadores de Tumor/genética , Carcinoma in Situ/genética , Carcinoma in Situ/patología , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidad , Carcinoma Ductal Pancreático/secundario , Diferenciación Celular , Línea Celular Tumoral , Núcleo Celular/metabolismo , Núcleo Celular/patología , Humanos , Inmunohistoquímica , Metástasis Linfática , Mucinas/genética , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Análisis de Matrices Tisulares
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