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 Show more
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. Show less