Gruop Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Universitat de les Illes Balears, 07122 Palma de Mallorca, Spain.
Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Hospital Universitario Son Espases, Edificio S, 07120 Palma de Mallorca, Spain.
Biomolecules. 2024 Oct 25;14(11):1359. doi: 10.3390/biom14111359.
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.
奥沙利铂成功地用于晚期结直肠癌以消灭微转移，但其在结直肠癌早期的益处仍存在争议，因为约 30%的患者出现意外复发。在此，我们评估氧化磷酸化为结直肠癌奥沙利铂反应预测生物标志物的疗效。我们发现无反应患者表现出低氧化磷酸化活性，提示预后不良。为了得出这个结论，我们分析了 GSE83129 数据集接受奥沙利铂治疗的患者样本，并用 ROCplotter 验证了一组数据集，根据他们对药物的反应选择了这些数据集。通过分析多种奥沙利铂耐药和敏感细胞系，我们确定氧化磷酸化 KEGG 途径是奥沙利铂反应的有价值的预测生物标志物，曲线下面积（AUC）为 0.843。此外，一些氧化磷酸化相关生物标志物在原发性和转移性衍生肿瘤球体中得到了验证，证实了计算机模拟的结果。这些生物标志物的低表达具有临床意义，表明总生存期和无复发生存期缩短，预后不良。本研究提出使用氧化磷酸化相关蛋白表达水平作为预测奥沙利铂为基础治疗反应的指标，以防止复发，并实现更个性化的治疗方法。我们的结果强调了氧化磷酸化为预测结直肠癌奥沙利铂治疗反应的可靠标志物的价值。
