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Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer

التفاصيل البيبلوغرافية
العنوان: Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer
المؤلفون: Elander, N. O., Aughton, K., Ghaneh, P., Neoptolemos, J. P., Palmer, D. H., Cox, T. F., Campbell, F., Costello, E., Halloran, C. M., Mackey, J. R., Scarfe, A. G., Valle, J. W., McDonald, A. C., Carter, R., Tebbutt, N. C., Goldstein, D., Shannon, J., Dervenis, C., Glimelius, Bengt, Deakin, M., Charnley, R. M., Anthoney, Alan, Lerch, M. M., Mayerle, J., Olah, A., Buechler, M. W., Greenhalf, W.
المصدر: British Journal of Cancer. 118(7):947-954
الوصف: Background: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy.Methods: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA).Results: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009).Conclusion: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.
وصف الملف: electronic
URL الوصول: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-351639
https://doi.org/10.1038/s41416-018-0004-2
https://uu.diva-portal.org/smash/get/diva2:1211627/FULLTEXT01.pdf
قاعدة البيانات: SwePub
الوصف
تدمد:00070920
15321827
DOI:10.1038/s41416-018-0004-2