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Association between miRNA expression profiles and polymorphisms of dihydropyrimidine dehydrogenase drug‑metabolizing gene in patients with colorectal cancer receiving 5‑fluorouracil

  • Authors:
    • Phatchariya Phannasil
    • Phichai Chansriwong
    • Ekaphop Sirachainan
    • Thanyanan Reungwetwattana
    • Pimonpan Jinda
    • Somthawin Aiempradit
    • Suwannee Sirilerttrakul
    • Chonlaphat Sukasem
    • Chalirmporn Atasilp
  • View Affiliations / Copyright

    Affiliations: Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand, Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand, Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand, Chulabhorn International College of Medicine, Thammasat University, Pathum Thani 12120, Thailand
    Copyright: © Phannasil et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 175
    |
    Published online on: September 11, 2025
       https://doi.org/10.3892/br.2025.2053
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Abstract

5‑Fluorouracil (5‑FU) is widely used for colorectal cancer (CRC) treatment. Its administration is challenged by wide variability in patient toxicity. Genetic polymorphisms in dihydropyrimidine dehydrogenase (DYPD) and circulating microRNAs (miRNAs) are promising biomarkers to predict 5‑FU‑associated toxicity. The present study aimed to assess the association between miRNA expression profiles, three DPYD polymorphisms (85T>C, 1627A>G, 1896T>C) and hematological toxicity in patients with CRC receiving 5‑FU. A total of 48 patients with CRC treated with 5‑FU‑based regimens were prospectively enrolled. Genotyping for DPYD 85T>C, 1627A>G and 1896T>C was performed by TaqMan Realtime PCR. Hematological toxicity was assessed by Common Terminology Criteria for Adverse Events v5.0 across two chemotherapy cycles. In a subset (n=9 for 85T>C; n=6 for 1896T>C), plasma levels of 43 candidate miRNAs related to 5‑FU metabolism were quantified using a custom miRNA PCR array. The variant allele frequencies of DPYD were 0.14 for both 85T>C and 1896T>C, and 0.17 for 1627A>G. Although no associations were significant, carriers of 85T>C exhibited a higher incidence of grade ≥1 anemia in cycle two (69.2 vs. 40.0%, TC and CC; P=0.070). No significant trends were observed for other toxicities. miRNA profiling revealed that 20 miRNAs were differentially expressed in 85T>C carriers (9 up‑ and 11 downregulated) and 14 miRNAs in 1896T>C carriers (5 up‑ and 9 downregulated) vs. wild‑type (P<0.05). The present findings suggest that the DPYD 85T>C polymorphism may predispose patients with CRC to cumulative hematological toxicity and is associated with distinct plasma miRNA signatures. Integration of DPYD genotyping with miRNA profiling warrants further investigation as a strategy to optimize 5‑FU dosing and minimize toxicity in CRC.
View Figures

Figure 1

miR expression profiles in patients
with VT (DPYD 85T>C) and WT colorectal cancer. A total of
43 miRs were detected in the plasma of patients with VT (n=4) and
WT colorectal cancer (n=5) using miR array. (A) Heat map of
differential expression of miRs in VT compared with WT colorectal
cancer. Red and green show up- and downregulation, respectively.
(B) Scatter plot showing miR profiles between VT and WT colorectal
cancer. Each dot represents the fold-change in expression of miRNA.
Red, green, and black dots represent up- and downregulated and
unchanged miRNAs, respectively. miR, microRNA; VT, Variant;
DPYD, dihydropyrimidine dehydrogenase gene; WT, Wild type;
min, minimum; avg, average; max, maximum; sn, small nuclear.

Figure 2

miRNA expression profiles in patients
with VT (DPYD 1896T>C) and WT colorectal cancer. A total
of 43 miRs were detected in the plasma of patients with (n=3) and
WT colorectal cancer (n=3). (A) Heat map of differential expression
of miRs in VT compared with WT colorectal cancer. Red and green
show up- and downregulation, respectively. (B) Scatter plot showing
miR profiles between VT and WT colorectal cancer. Each dot
represents the fold-change in expression of miRNA. Red, green, and
black dots represent up- and downregulated and unchanged miRNAs,
respectively. miR, microRNA; VT, Variant; DPYD,
dihydropyrimidine dehydrogenase gene; WT, Wild type; min, minimum;
avg, average; max, maximum; snRNA, small nuclear RNA.
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Copy and paste a formatted citation
Spandidos Publications style
Phannasil P, Chansriwong P, Sirachainan E, Reungwetwattana T, Jinda P, Aiempradit S, Sirilerttrakul S, Sukasem C and Atasilp C: Association between miRNA expression profiles and polymorphisms of dihydropyrimidine dehydrogenase drug‑metabolizing gene in patients with colorectal cancer receiving 5‑fluorouracil. Biomed Rep 23: 175, 2025.
APA
Phannasil, P., Chansriwong, P., Sirachainan, E., Reungwetwattana, T., Jinda, P., Aiempradit, S. ... Atasilp, C. (2025). Association between miRNA expression profiles and polymorphisms of dihydropyrimidine dehydrogenase drug‑metabolizing gene in patients with colorectal cancer receiving 5‑fluorouracil. Biomedical Reports, 23, 175. https://doi.org/10.3892/br.2025.2053
MLA
Phannasil, P., Chansriwong, P., Sirachainan, E., Reungwetwattana, T., Jinda, P., Aiempradit, S., Sirilerttrakul, S., Sukasem, C., Atasilp, C."Association between miRNA expression profiles and polymorphisms of dihydropyrimidine dehydrogenase drug‑metabolizing gene in patients with colorectal cancer receiving 5‑fluorouracil". Biomedical Reports 23.5 (2025): 175.
Chicago
Phannasil, P., Chansriwong, P., Sirachainan, E., Reungwetwattana, T., Jinda, P., Aiempradit, S., Sirilerttrakul, S., Sukasem, C., Atasilp, C."Association between miRNA expression profiles and polymorphisms of dihydropyrimidine dehydrogenase drug‑metabolizing gene in patients with colorectal cancer receiving 5‑fluorouracil". Biomedical Reports 23, no. 5 (2025): 175. https://doi.org/10.3892/br.2025.2053
Copy and paste a formatted citation
x
Spandidos Publications style
Phannasil P, Chansriwong P, Sirachainan E, Reungwetwattana T, Jinda P, Aiempradit S, Sirilerttrakul S, Sukasem C and Atasilp C: Association between miRNA expression profiles and polymorphisms of dihydropyrimidine dehydrogenase drug‑metabolizing gene in patients with colorectal cancer receiving 5‑fluorouracil. Biomed Rep 23: 175, 2025.
APA
Phannasil, P., Chansriwong, P., Sirachainan, E., Reungwetwattana, T., Jinda, P., Aiempradit, S. ... Atasilp, C. (2025). Association between miRNA expression profiles and polymorphisms of dihydropyrimidine dehydrogenase drug‑metabolizing gene in patients with colorectal cancer receiving 5‑fluorouracil. Biomedical Reports, 23, 175. https://doi.org/10.3892/br.2025.2053
MLA
Phannasil, P., Chansriwong, P., Sirachainan, E., Reungwetwattana, T., Jinda, P., Aiempradit, S., Sirilerttrakul, S., Sukasem, C., Atasilp, C."Association between miRNA expression profiles and polymorphisms of dihydropyrimidine dehydrogenase drug‑metabolizing gene in patients with colorectal cancer receiving 5‑fluorouracil". Biomedical Reports 23.5 (2025): 175.
Chicago
Phannasil, P., Chansriwong, P., Sirachainan, E., Reungwetwattana, T., Jinda, P., Aiempradit, S., Sirilerttrakul, S., Sukasem, C., Atasilp, C."Association between miRNA expression profiles and polymorphisms of dihydropyrimidine dehydrogenase drug‑metabolizing gene in patients with colorectal cancer receiving 5‑fluorouracil". Biomedical Reports 23, no. 5 (2025): 175. https://doi.org/10.3892/br.2025.2053
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