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



Elander, NO, Aughton, K ORCID: 0000-0002-5184-5789, Ghaneh, P, Neoptolemos, JP, Palmer, DH ORCID: 0000-0002-7147-5703, Cox, TF, Campbell, F, Costello-Goldring, E ORCID: 0000-0002-0104-8992, Halloran, CM ORCID: 0000-0002-5471-4178, Mackey, JR
et al (show 16 more authors) (2018) Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predict survival in pancreatic cancer. British Journal of Cancer, 118 (7). 947 - 954.

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Resubmission ms DPD 26-11-2017 NE.DOCX - Accepted Version

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: Cancer, Tumour biomarkers
Depositing User: Symplectic Admin
Date Deposited: 08 Jan 2018 15:18
Last Modified: 24 Jun 2021 11:04
DOI: 10.1038/s41416-018-0004-2
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3011037