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Title: | hENT1 Predicts Benefit from Gemcitabine in Pancreatic Cancer but Only with Low CDA mRNA. | Austin Authors: | Aughton, Karen;Elander, Nils O;Evans, Anthony;Jackson, Richard;Campbell, Fiona;Costello, Eithne;Halloran, Christopher M;Mackey, John R;Scarfe, Andrew G;Valle, Juan W;Carter, Ross;Cunningham, David;Tebbutt, Niall C ;Goldstein, David;Shannon, Jennifer;Glimelius, Bengt;Hackert, Thilo;Charnley, Richard M;Anthoney, Alan;Lerch, Markus M;Mayerle, Julia;Palmer, Daniel H;Büchler, Markus W;Ghaneh, Paula;Neoptolemos, John P;Greenhalf, William | Affiliation: | Prince of Wales Hospital and Clinical School, University of New South Wales, Sydney, NSW 2052, Australia Medizinische Klinik und Poliklinik II, Klinikum der LMU München-Grosshadern, 81377 München, Germany Department of Medicine A, University Medicine Greifswald, 17489 Greifswald, Germany Department of Oncology, Linköping University, SE-581 83 Linköping, Sweden Liverpool Experimental Cancer Medicine Centre, 2nd Floor Sherrington Building, Ashton St, University of Liverpool, Liverpool L69 3GE, UK Austin Health Liverpool Experimental Cancer Medicine Centre, 2nd Floor Sherrington Building, Ashton St, University of Liverpool, Liverpool L69 3GE, UK Nepean Cancer Centre, University of Sydney, Sydney, NSW 2747, Australia Liverpool Experimental Cancer Medicine Centre, 2nd Floor Sherrington Building, Ashton St, University of Liverpool, Liverpool L69 3GE, UK Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada The Christie NHS Foundation Trust, University of Manchester, Manchester M20 4BX, UK Glasgow Royal Infirmary, Glasgow G4 0SF, UK Royal Marsden National Health Service (NHS) Foundation Trust, London SW3 6JJ, UK Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 05 Uppsala, Sweden Department of Surgery, University of Heidelberg, 69047 Heidelberg, Germany Freeman Hospital, Newcastle upon Tyne NE7 7DN, UK St James's University Hospital, Leeds LS9 7TF, UK Department of Medicine A, University Medicine Greifswald, 17489 Greifswald, Germany Liverpool Experimental Cancer Medicine Centre, 2nd Floor Sherrington Building, Ashton St, University of Liverpool, Liverpool L69 3GE, UK Department of Surgery, University of Heidelberg, 69047 Heidelberg, Germany Liverpool Experimental Cancer Medicine Centre, 2nd Floor Sherrington Building, Ashton St, University of Liverpool, Liverpool L69 3GE, UK Department of Surgery, University of Heidelberg, 69047 Heidelberg, Germany Liverpool Experimental Cancer Medicine Centre, 2nd Floor Sherrington Building, Ashton St, University of Liverpool, Liverpool L69 3GE, UK |
Issue Date: | 17-Nov-2021 | Date: | 2021 | Publication information: | Cancers 2021; 13(22): 5758 | Abstract: | Gemcitabine or 5-fluorouracil (5-FU) based treatments can be selected for pancreatic cancer. Equilibrative nucleoside transporter 1 (hENT1) predicts adjuvant gemcitabine treatment benefit over 5-FU. Cytidine deaminase (CDA), inside or outside of the cancer cell, will deaminate gemcitabine, altering transporter affinity. ESPAC-3(v2) was a pancreatic cancer trial comparing adjuvant gemcitabine and 5-FU. Tissue microarray sections underwent in situ hybridization and immunohistochemistry. Analysis of both CDA and hENT1 was possible with 277 patients. The transcript did not correlate with protein levels for either marker. High hENT1 protein was prognostic with gemcitabine; median overall survival was 26.0 v 16.8 months (p = 0.006). Low CDA transcript was prognostic regardless of arm; 24.8 v 21.2 months with gemcitabine (p = 0.02) and 26.4 v 14.6 months with 5-FU (p = 0.02). Patients with low hENT1 protein did better with 5-FU, but only if the CDA transcript was low (median survival of 5-FU v gemcitabine; 29.3 v 18.3 months, compared with 14.2 v 14.6 with high CDA). CDA mRNA is an independent prognostic biomarker. When added to hENT1 protein status, it may also provide treatment-specific predictive information and, within the frame of a personalized treatment strategy, guide to either gemcitabine or 5FU for the individual patient. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/28224 | DOI: | 10.3390/cancers13225758 | ORCID: | 0000-0001-8547-1730 0000-0002-1999-0863 0000-0002-9643-8263 0000-0002-1865-3195 |
Journal: | Cancers | PubMed URL: | 34830914 | ISSN: | 2072-6694 | Type: | Journal Article | Subjects: | 5-fluorouracil biomarker chemotherapy gemcitabine predictive marker prognostic marker pyrimidine |
Appears in Collections: | Journal articles |
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