Oxidative Phosphorylation as a Predictive Biomarker of Oxaliplatin Response in Colorectal Cancer
Oxaliplatin is successfully used on advanced colorectal cancer to eradicate micro-metastasis, whereas its benefits in the early stages of colorectal cancer remains controversial since approximately 30% of patients experience unexpected relapses. Herein, we evaluate the efficacy of oxidative phosphor...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-10-01
|
| Series: | Biomolecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-273X/14/11/1359 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846154166353788928 |
|---|---|
| author | Toni Martinez-Bernabe Daniel G. Pons Jordi Oliver Jorge Sastre-Serra |
| author_facet | Toni Martinez-Bernabe Daniel G. Pons Jordi Oliver Jorge Sastre-Serra |
| author_sort | Toni Martinez-Bernabe |
| collection | DOAJ |
| description | Oxaliplatin is successfully used on advanced colorectal cancer to eradicate micro-metastasis, whereas its benefits in the early stages of colorectal cancer remains controversial since approximately 30% of patients experience unexpected relapses. Herein, we evaluate the efficacy of oxidative phosphorylation as a predictive biomarker of oxaliplatin response in colorectal cancer. We found that non-responding patients exhibit low oxidative phosphorylation activity, suggesting a poor prognosis. To reach this conclusion, we analyzed patient samples of individuals treated with oxaliplatin from the GSE83129 dataset, and a set of datasets validated using ROCplotter, selecting them based on their response to the drug. By analyzing multiple oxaliplatin-resistant and -sensitive cell lines, we identified oxidative phosphorylation KEGG pathways as a valuable predictive biomarker of oxaliplatin response with a high area under the curve (AUC = 0.843). Additionally, some oxidative phosphorylation-related biomarkers were validated in primary- and metastatic-derived tumorspheres, confirming the results obtained in silico. The low expression of these biomarkers is clinically relevant, indicating poor prognosis with decreased overall and relapse-free survival. This study proposes using oxidative phosphorylation-related protein expression levels as a predictor of responses to oxaliplatin-based treatments to prevent relapse and enable a more personalized therapy approach. Our results underscore the value of oxidative phosphorylation as a reliable marker for predicting the response to oxaliplatin treatment in colorectal cancer. |
| format | Article |
| id | doaj-art-44cacf3b6ace43e4b1e6729cc413f6b9 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-44cacf3b6ace43e4b1e6729cc413f6b92024-11-26T17:53:57ZengMDPI AGBiomolecules2218-273X2024-10-011411135910.3390/biom14111359Oxidative Phosphorylation as a Predictive Biomarker of Oxaliplatin Response in Colorectal CancerToni Martinez-Bernabe0Daniel G. Pons1Jordi Oliver2Jorge Sastre-Serra3Gruop Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, SpainGruop Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, SpainGruop Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, SpainGruop Multidisciplinar de Oncología Traslacional, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, SpainOxaliplatin is successfully used on advanced colorectal cancer to eradicate micro-metastasis, whereas its benefits in the early stages of colorectal cancer remains controversial since approximately 30% of patients experience unexpected relapses. Herein, we evaluate the efficacy of oxidative phosphorylation as a predictive biomarker of oxaliplatin response in colorectal cancer. We found that non-responding patients exhibit low oxidative phosphorylation activity, suggesting a poor prognosis. To reach this conclusion, we analyzed patient samples of individuals treated with oxaliplatin from the GSE83129 dataset, and a set of datasets validated using ROCplotter, selecting them based on their response to the drug. By analyzing multiple oxaliplatin-resistant and -sensitive cell lines, we identified oxidative phosphorylation KEGG pathways as a valuable predictive biomarker of oxaliplatin response with a high area under the curve (AUC = 0.843). Additionally, some oxidative phosphorylation-related biomarkers were validated in primary- and metastatic-derived tumorspheres, confirming the results obtained in silico. The low expression of these biomarkers is clinically relevant, indicating poor prognosis with decreased overall and relapse-free survival. This study proposes using oxidative phosphorylation-related protein expression levels as a predictor of responses to oxaliplatin-based treatments to prevent relapse and enable a more personalized therapy approach. Our results underscore the value of oxidative phosphorylation as a reliable marker for predicting the response to oxaliplatin treatment in colorectal cancer.https://www.mdpi.com/2218-273X/14/11/1359colorectal canceroxidative phosphorylationbiomarkersoxaliplatinresistance |
| spellingShingle | Toni Martinez-Bernabe Daniel G. Pons Jordi Oliver Jorge Sastre-Serra Oxidative Phosphorylation as a Predictive Biomarker of Oxaliplatin Response in Colorectal Cancer Biomolecules colorectal cancer oxidative phosphorylation biomarkers oxaliplatin resistance |
| title | Oxidative Phosphorylation as a Predictive Biomarker of Oxaliplatin Response in Colorectal Cancer |
| title_full | Oxidative Phosphorylation as a Predictive Biomarker of Oxaliplatin Response in Colorectal Cancer |
| title_fullStr | Oxidative Phosphorylation as a Predictive Biomarker of Oxaliplatin Response in Colorectal Cancer |
| title_full_unstemmed | Oxidative Phosphorylation as a Predictive Biomarker of Oxaliplatin Response in Colorectal Cancer |
| title_short | Oxidative Phosphorylation as a Predictive Biomarker of Oxaliplatin Response in Colorectal Cancer |
| title_sort | oxidative phosphorylation as a predictive biomarker of oxaliplatin response in colorectal cancer |
| topic | colorectal cancer oxidative phosphorylation biomarkers oxaliplatin resistance |
| url | https://www.mdpi.com/2218-273X/14/11/1359 |
| work_keys_str_mv | AT tonimartinezbernabe oxidativephosphorylationasapredictivebiomarkerofoxaliplatinresponseincolorectalcancer AT danielgpons oxidativephosphorylationasapredictivebiomarkerofoxaliplatinresponseincolorectalcancer AT jordioliver oxidativephosphorylationasapredictivebiomarkerofoxaliplatinresponseincolorectalcancer AT jorgesastreserra oxidativephosphorylationasapredictivebiomarkerofoxaliplatinresponseincolorectalcancer |