Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study.
BACKGROUND:Adjuvant chemotherapy for colorectal cancer is mainly based on the combination of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4). The pharmacological target of oxaliplatin remains intracellular and therefore dependent on its entry into cells. The intracellular distribution of oxa...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4747515?pdf=render |
| _version_ | 1828526981224857600 |
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| author | Bertrand Le Roy Lucie Tixier Bruno Pereira Pierre Sauvanet Emmanuel Buc Caroline Pétorin Pierre Déchelotte Denis Pezet David Balayssac |
| author_facet | Bertrand Le Roy Lucie Tixier Bruno Pereira Pierre Sauvanet Emmanuel Buc Caroline Pétorin Pierre Déchelotte Denis Pezet David Balayssac |
| author_sort | Bertrand Le Roy |
| collection | DOAJ |
| description | BACKGROUND:Adjuvant chemotherapy for colorectal cancer is mainly based on the combination of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4). The pharmacological target of oxaliplatin remains intracellular and therefore dependent on its entry into cells. The intracellular distribution of oxaliplatin is mediated by organic cation transporters 1, 2 and 3 (OCT1, 2 and 3), copper transporter 1 (CTR1) and ATPase Cu2+ transporting beta polypeptide (ATP7B) and may modulate the efficacy of oxaliplatin-based chemotherapy. The aim of this study was to perform a retrospective study to assess the relation between the expression of oxaliplatin transporters in colorectal cancer before chemotherapy and the response to FOLFOX-4 adjuvant chemotherapy in responder and non-responder patients. METHODS:This retrospective study was conducted at a single center (University Hospital of Clermont-Ferrand, France). The target population was patients with resectable colorectal cancer operated between 2006 and 2013. Inclusion criteria were defined for the responder patients as no cancer recurrence 3 years after the end of chemotherapy, and for the non-responder patients as cancer recurrence within 1 year. Other inclusion criteria were stages IIb-IV cancers, first-line adjuvant FOLFOX-4 chemotherapy, and the availability of resected primary tumor samples. Exclusion criteria were preoperative chemotherapy and/or radiotherapy, a targeted therapy, other anticancer drugs, cancer recurrence between the first and the third year after the end of chemotherapy and follow-up < 3 years. Immunostaining of oxaliplatin transporters (OCT1, 2, 3, CTR1 and ATP7B) and Ki-67 was assessed in tumor samples. RESULTS:Retrospectively, 31 patients have been selected according to inclusion and exclusion criteria (15 responders and 16 non-responders). Before FOLFOX-4 regimen, OCT3 expression was significantly lower in responder patients compared to non-responders (p<0.001). According to multivariate analysis, OCT3 remains an independent criterion for adjuvant FOLFOX chemotherapy response (p = 0.039). No significant relation is reported between chemotherapy response and the expression of OCT1 (p = 0.49), OCT2 (p = 0.09), CTR1 (p = 0.45), ATP7B (p = 0.94) and Ki-67 (p = 0.34) in tumors. CONCLUSIONS:High expression of OCT3 could be an independent factor related to resistance to FOLFOX-4 chemotherapy. |
| first_indexed | 2024-12-11T21:32:37Z |
| format | Article |
| id | doaj.art-d17c60f5487a409bb42c2e2980f33a2a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T21:32:37Z |
| publishDate | 2016-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-d17c60f5487a409bb42c2e2980f33a2a2022-12-22T00:50:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01112e014873910.1371/journal.pone.0148739Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study.Bertrand Le RoyLucie TixierBruno PereiraPierre SauvanetEmmanuel BucCaroline PétorinPierre DéchelotteDenis PezetDavid BalayssacBACKGROUND:Adjuvant chemotherapy for colorectal cancer is mainly based on the combination of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4). The pharmacological target of oxaliplatin remains intracellular and therefore dependent on its entry into cells. The intracellular distribution of oxaliplatin is mediated by organic cation transporters 1, 2 and 3 (OCT1, 2 and 3), copper transporter 1 (CTR1) and ATPase Cu2+ transporting beta polypeptide (ATP7B) and may modulate the efficacy of oxaliplatin-based chemotherapy. The aim of this study was to perform a retrospective study to assess the relation between the expression of oxaliplatin transporters in colorectal cancer before chemotherapy and the response to FOLFOX-4 adjuvant chemotherapy in responder and non-responder patients. METHODS:This retrospective study was conducted at a single center (University Hospital of Clermont-Ferrand, France). The target population was patients with resectable colorectal cancer operated between 2006 and 2013. Inclusion criteria were defined for the responder patients as no cancer recurrence 3 years after the end of chemotherapy, and for the non-responder patients as cancer recurrence within 1 year. Other inclusion criteria were stages IIb-IV cancers, first-line adjuvant FOLFOX-4 chemotherapy, and the availability of resected primary tumor samples. Exclusion criteria were preoperative chemotherapy and/or radiotherapy, a targeted therapy, other anticancer drugs, cancer recurrence between the first and the third year after the end of chemotherapy and follow-up < 3 years. Immunostaining of oxaliplatin transporters (OCT1, 2, 3, CTR1 and ATP7B) and Ki-67 was assessed in tumor samples. RESULTS:Retrospectively, 31 patients have been selected according to inclusion and exclusion criteria (15 responders and 16 non-responders). Before FOLFOX-4 regimen, OCT3 expression was significantly lower in responder patients compared to non-responders (p<0.001). According to multivariate analysis, OCT3 remains an independent criterion for adjuvant FOLFOX chemotherapy response (p = 0.039). No significant relation is reported between chemotherapy response and the expression of OCT1 (p = 0.49), OCT2 (p = 0.09), CTR1 (p = 0.45), ATP7B (p = 0.94) and Ki-67 (p = 0.34) in tumors. CONCLUSIONS:High expression of OCT3 could be an independent factor related to resistance to FOLFOX-4 chemotherapy.http://europepmc.org/articles/PMC4747515?pdf=render |
| spellingShingle | Bertrand Le Roy Lucie Tixier Bruno Pereira Pierre Sauvanet Emmanuel Buc Caroline Pétorin Pierre Déchelotte Denis Pezet David Balayssac Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study. PLoS ONE |
| title | Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study. |
| title_full | Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study. |
| title_fullStr | Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study. |
| title_full_unstemmed | Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study. |
| title_short | Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study. |
| title_sort | assessment of the relation between the expression of oxaliplatin transporters in colorectal cancer and response to folfox 4 adjuvant chemotherapy a case control study |
| url | http://europepmc.org/articles/PMC4747515?pdf=render |
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