Prognostic value of folate-associated gene expression in stage II colon cancer

Abstract Purpose Prognostic variability in stage II colon cancer underscores the need for better risk stratification. Analyzing folate-associated gene expression in stage II colon cancer could provide researchers and clinicians with deeper insights into tumor biology and potentially aid in identifyi...

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Main Authors: Donia Kaidi, Elisabeth Odin, Yvonne Wettergren, Elinor Bexe Lindskog
Format: Article
Language:English
Published: Springer 2025-02-01
Series:Journal of Cancer Research and Clinical Oncology
Subjects:
Online Access:https://doi.org/10.1007/s00432-025-06141-w
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author Donia Kaidi
Elisabeth Odin
Yvonne Wettergren
Elinor Bexe Lindskog
author_facet Donia Kaidi
Elisabeth Odin
Yvonne Wettergren
Elinor Bexe Lindskog
author_sort Donia Kaidi
collection DOAJ
description Abstract Purpose Prognostic variability in stage II colon cancer underscores the need for better risk stratification. Analyzing folate-associated gene expression in stage II colon cancer could provide researchers and clinicians with deeper insights into tumor biology and potentially aid in identifying early prognostic and/or predictive biomarkers. Methods Patients with stage II colon cancer and recurrence (n = 48) were matched to patients with a 5 year recurrence-free follow-up (n = 133). Gene expression of ABCC3, AMT, FPGS, GGH, MFT, PCFT, RFC-1, and TYMS was analyzed in tumor tissue and matching colon mucosa using qPCR and evaluated in relation to time to recurrence (TTR), as well as to demographic and clinicopathological variables. Results Independent of other covariates, TYMS expression in tumors, pT4 stage, and emergency surgery were associated with TTR. There were significant differences in expression levels of all examined genes between tumor and mucosa. ABCC3, GGH, and RFC-1 expression levels differed in mucosa between microsatellite instability-high (MSI-H) compared to microsatellite stable/microsatellite instability-low (MSS/MSI-L) tumors, whereas tumoral expression of AMT, GGH, and TYMS differed between MSI-H and MSS/MSI-L tumors. Depending on tumor location, the expression of ABCC3, AMT, GGH, and RFC-1 in mucosa, as well as the tumoral expression of AMT, GGH, PCFT and RFC-1 differed. Conclusion Low tumoral expression of TYMS was associated with worse TTR, independent of MSI status, pT stage, and emergency surgery. The indication of a better outcome for patients with MSI-H status and high tumoral TYMS expression might be of particular interest in the stratification of patients for immunotherapy.
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spelling doaj-art-68a9b12e7a0348bb8dfe5e8151c9a28e2025-08-20T03:01:54ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352025-02-01151211110.1007/s00432-025-06141-wPrognostic value of folate-associated gene expression in stage II colon cancerDonia Kaidi0Elisabeth Odin1Yvonne Wettergren2Elinor Bexe Lindskog3Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of GothenburgDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of GothenburgDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of GothenburgDepartment of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of GothenburgAbstract Purpose Prognostic variability in stage II colon cancer underscores the need for better risk stratification. Analyzing folate-associated gene expression in stage II colon cancer could provide researchers and clinicians with deeper insights into tumor biology and potentially aid in identifying early prognostic and/or predictive biomarkers. Methods Patients with stage II colon cancer and recurrence (n = 48) were matched to patients with a 5 year recurrence-free follow-up (n = 133). Gene expression of ABCC3, AMT, FPGS, GGH, MFT, PCFT, RFC-1, and TYMS was analyzed in tumor tissue and matching colon mucosa using qPCR and evaluated in relation to time to recurrence (TTR), as well as to demographic and clinicopathological variables. Results Independent of other covariates, TYMS expression in tumors, pT4 stage, and emergency surgery were associated with TTR. There were significant differences in expression levels of all examined genes between tumor and mucosa. ABCC3, GGH, and RFC-1 expression levels differed in mucosa between microsatellite instability-high (MSI-H) compared to microsatellite stable/microsatellite instability-low (MSS/MSI-L) tumors, whereas tumoral expression of AMT, GGH, and TYMS differed between MSI-H and MSS/MSI-L tumors. Depending on tumor location, the expression of ABCC3, AMT, GGH, and RFC-1 in mucosa, as well as the tumoral expression of AMT, GGH, PCFT and RFC-1 differed. Conclusion Low tumoral expression of TYMS was associated with worse TTR, independent of MSI status, pT stage, and emergency surgery. The indication of a better outcome for patients with MSI-H status and high tumoral TYMS expression might be of particular interest in the stratification of patients for immunotherapy.https://doi.org/10.1007/s00432-025-06141-wCancerBiomarkerColorectal NeoplamsPrognosisFolic acidThymidylate synthase
spellingShingle Donia Kaidi
Elisabeth Odin
Yvonne Wettergren
Elinor Bexe Lindskog
Prognostic value of folate-associated gene expression in stage II colon cancer
Journal of Cancer Research and Clinical Oncology
Cancer
Biomarker
Colorectal Neoplams
Prognosis
Folic acid
Thymidylate synthase
title Prognostic value of folate-associated gene expression in stage II colon cancer
title_full Prognostic value of folate-associated gene expression in stage II colon cancer
title_fullStr Prognostic value of folate-associated gene expression in stage II colon cancer
title_full_unstemmed Prognostic value of folate-associated gene expression in stage II colon cancer
title_short Prognostic value of folate-associated gene expression in stage II colon cancer
title_sort prognostic value of folate associated gene expression in stage ii colon cancer
topic Cancer
Biomarker
Colorectal Neoplams
Prognosis
Folic acid
Thymidylate synthase
url https://doi.org/10.1007/s00432-025-06141-w
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AT elinorbexelindskog prognosticvalueoffolateassociatedgeneexpressioninstageiicoloncancer