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

建立人类平衡核苷转运蛋白-1与影响吉西他滨治疗反应的其他因素之间的相互作用模型,以预测胰腺导管腺癌患者的临床结果

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作者:Francesca Tavano, Andrea Fontana, Fabio Pellegrini, Francesca Paola Burbaci, Francesca Rappa, Francesco Cappello, Massimiliano Copetti, Evaristo Maiello, Lucia Lombardi, Paolo Graziano, Manlio Vinciguerra, Fabio Francesco di Mola, Pierluigi di Sebastiano, Angelo Andriulli, Valerio Pazienza

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.

Conclusion

hENT1, CHOP, MRP1 and DCK appear correlated to PDAC, and this interaction might influence disease behavior.

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.

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