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Towards Precision Oncology: A Predictive Nomogram Incorporating DPD and MTHFR for CapeOX Neoadjuvant Chemotherapy in
Elvida Christy Imelda Tahiya1, Ronald Erasio Lusikooy1, Ilhamjaya Pattelongi1
1Division of Digestive Surgery, Department of Surgery, Wahidin Sudirohusodo Hospital, Makassar, Indonesia.
Background:
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Variability in patient response to fluoropyrimidine-based neoadjuvant chemotherapy remains a critical challenge. We aimed to develop a nomogram that integrated dihydropyrimidine dehydrogenase (DPD) and methylenetetrahydrofolate reductase (MTHFR) expression to predict CapeOX (Capecitabine-Oxaliplatin) neoadjuvant chemotherapy outcomes in colorectal cancer.
Methods:
A prospective cohort of 36 advanced-stage CRC patients who received CapeOX neoadjuvant chemotherapy at Wahidin Sudirohusodo Hospital from 2024 to 2025 was analyzed. mRNA expression levels of TS, DPD, and MTHFR were measured in tissue and blood using quantitative RT-PCR. The chemotherapy response was evaluated by RECIST 1.1. Statistical analysis was performed to identify predictors of response, which were incorporated into a nomogram with bootstrap validation.
Results:
Among the 36 patients with advanced colorectal cancer, response to CapeOX chemotherapy was observed in 50%. Blood-based gene profiling revealed that responders had significantly lower DPD and MTHFR expression compared with non-responders (both p<0.001), while TS showed no predictive relevance. A nomogram that integrated only blood DPD and MTHFR achieved outstanding discrimination (AUC 0.932, C-index 0.78) and demonstrated strong calibration, accurately predicting treatment response across probability ranges. These results established circulating DPD and MTHFR as powerful non-invasive biomarkers and validated the nomogram as a robust tool for individualized response prediction.
Conclusion:
A predictive nomogram that incorporated DPD and MTHFR has improved individualized estimation of CapeOX neoadjuvant chemotherapy response in CRC, supporting precision oncology strategies.
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