Modeling interactions between Human Equilibrative Nucleoside Transporter-1 and other factors involved in the response to gemcitabine treatment to predict clinical outcomes in pancreatic ductal adenocarcinoma patients

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• 作者：Francesca Tavano (1)
  Andrea Fontana (2)
  Fabio Pellegrini (2) (3)
  Francesca Paola Burbaci (1)
  Francesca Rappa (4) (5)
  Francesco Cappello (4) (5)
  Massimiliano Copetti (2)
  Evaristo Maiello (6)
  Lucia Lombardi (6)
  Paolo Graziano (7)
  Manlio Vinciguerra (1) (4) (8)
  Fabio Francesco di Mola (9)
  Pierluigi di Sebastiano (9)
  Angelo Andriulli (1)
  Valerio Pazienza (1)
  
  1. Gastroenterology Unit ; I.R.C.C.S. 鈥淐asa Sollievo della Sofferenza鈥?Hospital San Giovanni Rotondo (FG) Italy ; viale dei Cappuccini n.1 ; San Giovanni Rotondo ; FG ; 71013 ; Italy
  2. Unit of Biostatistics I.R.C.C.S. 鈥淐asa Sollievo della Sofferenza鈥?Hospital San Giovanni Rotondo (FG) Italy ; viale dei Cappuccini n.1 ; San Giovanni Rotondo ; FG ; 71013 ; Italy
  3. Unit of Biostatistics ; DCPE ; Consorzio Mario Negri Sud ; Santa Maria Imbaro ; CH ; Italy
  4. Euro-Mediterranean Institute of Science and Technology ; Palermo ; Italy
  5. Department of Experimental Biomedicine and Clinical Neuroscience ; University of Palermo ; Palermo ; Italy
  6. Oncology Unit I.R.C.C.S. 鈥淐asa Sollievo della Sofferenza鈥?Hospital San Giovanni Rotondo (FG) Italy ; viale dei Cappuccini n.1 ; San Giovanni Rotondo ; FG ; 71013 ; Italy
  7. Pathology Unit I.R.C.C.S. 鈥淐asa Sollievo della Sofferenza鈥?Hospital San Giovanni Rotondo (FG) Italy ; viale dei Cappuccini n.1 ; San Giovanni Rotondo ; FG ; 71013 ; Italy
  8. University College London ; Institute for Liver and Digestive Health ; Division of Medicine ; Royal Free Campus ; London ; UK
  9. Division of Surgical Oncology 鈥淪S Annunziata鈥?Hospital ; Chieti ; Italy
  
• 关键词：Pancreatic ductal adenocarcinoma ; hENT1 ; CHOP ; MRP1 ; DCK ; RECPAM
• 刊名：Journal of Translational Medicine
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：12
• 期：1
• 全文大小：1,545 KB
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• 刊物主题：Biomedicine general; Medicine/Public Health, general;
• 出版者：BioMed Central
• ISSN：1479-5876

文摘

Background Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by largely unsatisfactory responses to the currently available therapeutic strategies. In this study we evaluated the expression of genes involved in gemcitabine uptake in a selected cohort of patients with PDAC, with well-defined clinical-pathological features. Methods mRNA levels of hENT1, CHOP, MRP1 and DCK were evaluated by means of qRT-PCR in matched pairs of tumor and adjacent normal tissue samples collected from PDAC patients treated with gemcitabine after surgical tumor resection. To detect possible interaction between gene expression levels and to identify subgroups of patients at different mortality/progression risk, the RECursive Partitioning and Amalgamation (RECPAM) method was used. Results RECPAM analysis showed that DCK and CHOP were most relevant variables for the identification of patients with different mortality risk, while hENT1 and CHOP were able to identify subgroups of patients with different disease progression risk. Conclusion: hENT1, CHOP, MRP1 and DCK appear correlated to PDAC, and this interaction might influence disease behavior.