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. 2025 Nov;21(26):3425-3434.
doi: 10.1080/14796694.2025.2567845. Epub 2025 Oct 5.

Prognostic implications of cancer-associated fibroblasts and desmoplastic reaction in stage III colon cancer risk groups

Nazım Can Demircan  1 , Mehmet Fatih Tekin  2 , Tuğba Akın Telli  1 , Rukiye Arıkan  1 , Tuğba Başoğlu  1 , Abdussamet Çelebi  1 , Alper Yaşar  1 , Selver Işık  1 , Özlem Ercelep  1 , Faysal Dane  1 , Çiğdem Ataizi Çelikel  2 , Perran Fulden Yumuk  1
Affiliations

Prognostic implications of cancer-associated fibroblasts and desmoplastic reaction in stage III colon cancer risk groups

Nazım Can Demircan et al. Future Oncol. 2025 Nov.

Abstract

Aim: Risk stratification is used to tailor adjuvant treatment in stage III colon cancer. Cancer associated fibroblasts (CAFs) and desmoplastic reaction (DR) contribute to tumor microenvironment and are associated with tumor progression. We aimed to assess the prognostic value of CAF markers and DR pattern in stage III colon cancer risk groups.

Materials and methods: Patients with curative surgery for stage III colon cancer were categorized as low-risk (pT1-3 and pN1) and high-risk (pT4 or pN2). Expressions of fibroblast activation protein α (FAPα), fibroblast specific protein-1 (S100A4) and α-smooth muscle actin (α-SMA) were evaluated semiquantitatively with H-scores. DR pattern was classified as immature, intermediate and mature. Cox regression models were used to determine hazard ratios (HRs) of prognostic factors.

Results: Within the study cohort (n = 172), 98 patients had high-risk and 74 had low-risk disease. In the low-risk group, high FAPα expression independently predicted DFS (HR = 3.06, p = 0.02). In the high-risk group, immature DR was an independent prognostic factor for both DFS (HR = 1.99, p = 0.02) and OS (HR = 2.04, p = 0.02).

Conclusion: FAPα as a surrogate marker of CAFs and DR pattern may have distinct prognostic impacts in stage III colon cancer risk groups and be utilized to refine prognosis further in these patients.

Keywords: Cancer-associated fibroblast; colon cancer; desmoplastic reaction; prognosis; tumor microenvironment.

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Conflict of interest statement

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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