Skip to content
DraconiticResearch
Search Sources API
201,818 studies31 sourcesUpdated 16 min ago
Peer-reviewedCC BY-NC 4.0Asian Pacific Journal of Cancer Prevention : APJCP

Blood-Based vs. Tissue-Based mRNA Expression of Thymidylate Synthase, Dihydropyrimidine Dehydrogenase, and Methylenetetrahydrofolate Reductase: A Prospective Study to Predict the Neoadjuvant CAPEOX Response in Advanced Colorectal Cancer

  • Elvida Christi Imelda Tahiya1
  • Ronald Erasio Lusikooy1,2,3
  • Ilhamjaya Patelongi4
  • Warsinggih Warsinggih1,2,3
  • Julianus Aboyaman Uwuratuw1
  • Erwin Syarifuddin1
  • Ibrahim Labeda1,2,3
  • Samuel Sampetoding1,2
  • Muhammad Ihwan Kusuma1,2
  • Muhammad Faruk3,5
5 affiliations
  1. 1Division of Digestive Surgery, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
  2. 2Dr Wahidin Sudirohusodo Hospital, Makassar, Indonesia.
  3. 3Hasanuddin University Hospital, Makassar, Indonesia.
  4. 4Department of Physiology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
  5. 5Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.
Read full textPDFDOICite

Abstract

Background:: Fluoropyrimidine-based chemotherapy is a fundamental treatment for colorectal cancer (CRC), yet its therapeutic efficacy is often limited by significant inter-individual variability. Enzymes involved in 5-fluorouracil (5-FU) metabolism thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and methylenetetrahydrofolate reductase (MTHFR) are critical determinants of drug response. This study aimed to evaluate the molecular correlation between TS, DPD, and MTHFR mRNA expression in paired tumor tissue and peripheral blood samples, while simultaneously developing and validating a non-invasive predictive nomogram to forecast therapeutic response to neoadjuvant CAPEOX (capecitabine–oxaliplatin) chemotherapy in advanced CRC.

Methods:: A prospective cohort study was conducted on 36 patients with stage III–IV CRC receiving CAPEOX. mRNA expression of TS, DPD, and MTHFR was quantified using qRT-PCR from paired tumor and peripheral blood samples. Chemotherapy response was evaluated using RECIST 1.1 criteria. Statistical analyses included Spearman correlation, the Mann–Whitney U test, and multivariate logistic regression. A nomogram was constructed based on significant predictors.

Results:: DPD and MTHFR expression levels were significantly lower in responders than in non-responders (p < 0.001), while TS expression showed no significant difference. Gene expression in tissue and blood was strongly correlated (r = 0.820 for TS, r = 0.658 for DPD, and r = 0.623 for MTHFR; all p < 0.001). Multivariate analysis identified blood-based DPD and MTHFR expression as independent predictors of response. The predictive nomogram demonstrated excellent discrimination (AUC = 0.932).

Conclusion:: Lower DPD and MTHFR expression predicts a favorable response to neoadjuvant CAPEOX in advanced CRC. These biomarkers offer a promising, non-invasive approach to personalizing treatment strategies potentially enhancing therapeutic efficacy while minimizing unnecessary toxicity.

Related

  1. MH-Penile-002: a phase II, prospective, single-arm trial of neoadjuvant anti-EGFR antibody-drug conjugate plus PD-1 inhibitor in penile cancer with challenging penile preservation or regional lymph node metastasis
    Jia-Yao Wang, Yan-Xiang Shao, Li-Li Yang +6
    Future OncologyPeer-reviewedLicence not statedFull textSurgery & anaesthesiaPMC
  2. Patient-reported Symptom Resolution After Neoadjuvant Versus Adjuvant Chemotherapy for Early Breast Cancer: A Prospective Observational Cohort Study
    TAKAAKI FUJII, KEI ICHIBA, MAYU AOKI +4
    In VivoPeer-reviewedCC BY-NC-ND 4.0Full textOncologyPMC
  3. Outcomes of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer: A Prospective Observational Real-World Cohort in Johannesburg, South Africa
    S. Amod, M. Tunmer, L. Campbell-Roper +6
    medRxivPreprintCC BYFull textOncologymedRxiv
  4. Anterior Uveitis in Patients With Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms: A Case Series
    Nancy Zakaria, Caroline A Tawfik, Samir Shoughy
    CureusPeer-reviewedCC BYFull textGeneral medicineEurope PMCPMC
  5. Role of Paternal Methylenetetrahydrofolate Reductase Polymorphisms on Recurrent Pregnancy Loss and In vitro Fertilisation Outcomes: A Systematic Review and Meta analysis.
    Kuky Cahya Hamurajib, Mawaddah Ar Rochmah, Dhite Bayu Nugroho +2
    Journal of human reproductive sciencesPeer-reviewedCC BY-NC-SAFull textGeneral medicineEurope PMC

Cite

BibTeXRIS
BibTeX
@article{tahiya2026bloodbased,
  title = {{Blood-Based vs. Tissue-Based mRNA Expression of Thymidylate Synthase, Dihydropyrimidine Dehydrogenase, and Methylenetetrahydrofolate Reductase: A Prospective Study to Predict the Neoadjuvant CAPEOX Response in Advanced Colorectal Cancer}},
  author = {Elvida Christi Imelda Tahiya and Ronald Erasio Lusikooy and Ilhamjaya Patelongi and Warsinggih Warsinggih and Julianus Aboyaman Uwuratuw and Erwin Syarifuddin and Ibrahim Labeda and Samuel Sampetoding and Muhammad Ihwan Kusuma and Muhammad Faruk},
  journal = {Asian Pacific Journal of Cancer Prevention : APJCP},
  year = {2026},
  month = jun,
  doi = {10.31557/apjcp.2026.27.6.2269},
  url = {https://doi.org/10.31557/apjcp.2026.27.6.2269},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Blood-Based vs. Tissue-Based mRNA Expression of Thymidylate Synthase, Dihydropyrimidine Dehydrogenase, and Methylenetetrahydrofolate Reductase: A Prospective Study to Predict the Neoadjuvant CAPEOX Response in Advanced Colorectal Cancer
AU  - Elvida Christi Imelda Tahiya
AU  - Ronald Erasio Lusikooy
AU  - Ilhamjaya Patelongi
AU  - Warsinggih Warsinggih
AU  - Julianus Aboyaman Uwuratuw
AU  - Erwin Syarifuddin
AU  - Ibrahim Labeda
AU  - Samuel Sampetoding
AU  - Muhammad Ihwan Kusuma
AU  - Muhammad Faruk
PY  - 2026
DA  - 2026/06/21
JO  - Asian Pacific Journal of Cancer Prevention : APJCP
DO  - 10.31557/apjcp.2026.27.6.2269
UR  - https://doi.org/10.31557/apjcp.2026.27.6.2269
AB  - Background:: Fluoropyrimidine-based chemotherapy is a fundamental treatment for colorectal cancer (CRC), yet its therapeutic efficacy is often limited by significant inter-individual variability. Enzymes involved in 5-fluorouracil (5-FU) metabolism thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and methylenetetrahydrofolate reductase (MTHFR) are critical determinants of drug response. This study aimed to evaluate the molecular correlation between TS, DPD, and MTHFR mRNA expression in paired tumor tissue and peripheral blood samples, while simultaneously developing and validating a non-invasive predictive nomogram to forecast therapeutic response to neoadjuvant CAPEOX (capecitabine–oxaliplatin) chemotherapy in advanced CRC.  Methods:: A prospective cohort study was conducted on 36 patients with stage III–IV CRC receiving CAPEOX. mRNA expression of TS, DPD, and MTHFR was quantified using qRT-PCR from paired tumor and peripheral blood samples. Chemotherapy response was evaluated using RECIST 1.1 criteria. Statistical analyses included Spearman correlation, the Mann–Whitney U test, and multivariate logistic regression. A nomogram was constructed based on significant predictors.  Results:: DPD and MTHFR expression levels were significantly lower in responders than in non-responders (p < 0.001), while TS expression showed no significant difference. Gene expression in tissue and blood was strongly correlated (r = 0.820 for TS, r = 0.658 for DPD, and r = 0.623 for MTHFR; all p < 0.001). Multivariate analysis identified blood-based DPD and MTHFR expression as independent predictors of response. The predictive nomogram demonstrated excellent discrimination (AUC = 0.932).  Conclusion:: Lower DPD and MTHFR expression predicts a favorable response to neoadjuvant CAPEOX in advanced CRC. These biomarkers offer a promising, non-invasive approach to personalizing treatment strategies potentially enhancing therapeutic efficacy while minimizing unnecessary toxicity.
SN  - 1513-7368
SN  - 2476-762X
ER  -