Dynamic Changes and Prognostic Significance of Serum Soluble TIM-3 and IFN-γ/IL-10 after Radiofrequency Ablation of Solitary Liver Metastases in Colorectal Cancer

Jingjing LIU; Juan LIU; Xinhong LI; Peidong HE; Yingchun WANG; Jie SHAO

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Jingjing LIU, Juan LIU, Xinhong LI, Peidong HE, Yingchun WANG, Jie SHAO. Dynamic Changes and Prognostic Significance of Serum Soluble TIM-3 and IFN-γ/IL-10 after Radiofrequency Ablation of Solitary Liver Metastases in Colorectal Cancer[J]. Journal of Kunming Medical University.

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Dynamic Changes and Prognostic Significance of Serum Soluble TIM-3 and IFN-γ/IL-10 after Radiofrequency Ablation of Solitary Liver Metastases in Colorectal Cancer

1.
Department of Oncology and Hematology
2.
Department of Respiratory and Critical Care Medicine，Ordnance Industry General Hospital，Xi'an Shaanxi 710065，China

Received Date: 2026-03-20

Abstract

Abstract

Objective To investigate the dynamic changes and prognostic significance of serum soluble T cell immunoglobulin and mucin domain containing 3 （sTIM-3） and the interferon-γ/interleukin-10 ratio （IFN-γ/IL-10） after radiofrequency ablation （RFA） of solitary liver metastases from colorectal cancer. Methods A total of 137 patients with solitary colorectal cancer liver metastases who underwent RFA with curative intent between December 2021 and December 2023 were prospectively enrolled. sTIM-3, IFN-γ, and IL-10 were measured at multiple time points—24 hours before ablation and 24 hours, 7 days, 1 month, 3 months, 6 months, 12 months, and 24 months after ablation—and the IFN-γ/IL-10 ratio was calculated. Follow-up continued until December 31, 2025. With recurrence as the primary outcome, linear mixed-effects models were used to assess dynamic changes, while logistic regression and Cox proportional hazards models were used to identify factors associated with recurrence and recurrence-free survival （RFS）. Results With a median follow-up of 22.40 months, recurrence occurred in 46 patients （33.58%） and death in 12 （8.76%）; the 2-year RFS rate was 66.90%. At baseline, the recurrence group had a larger maximum diameter of liver metastases than the non-recurrence group （31.37±9.08 mm vs 25.55±7.79 mm, t = 3.720, P < 0.001）, a higher proportion of ablation margins <5 mm （43.48% vs 20.88%, χ² = 7.640, P = 0.006）, a higher proportion of elevated CEA （45.65% vs 21.98%, χ² = 8.190, P = 0.004）, higher sTIM-3 levels （478.42±132.69 pg/mL vs 378.88±110.57 pg/mL, t = 4.610, P < 0.001）, and a lower IFN-γ/IL-10 ratio （1.81±0.92 vs 2.71±1.04, t = 5.210, P < 0.001）. Dynamic analysis showed that after early postoperative fluctuation, sTIM-3 continuously increased from 1 month postoperatively in the recurrence group but gradually declined in the non-recurrence group, with a significant time-by-recurrence-outcome interaction （F = 5.240, P = 0.002）. At 1 month postoperatively, the IFN-γ/IL-10 ratio was significantly lower in the recurrence group than in the non-recurrence group （1.70±0.80 vs 2.80±1.00, t = 6.020, P < 0.001）. Multivariate logistic regression showed that an increased maximum diameter of liver metastases （OR = 1.06, 95%CI: 1.02～1.11, P = 0.003）, ablation margin <5 mm （OR = 2.21, 95%CI: 1.06～4.60, P = 0.036）, elevated CEA （OR = 1.98, 95%CI: 1.00～3.92, P = 0.048）, elevated sTIM-3 （OR = 1.04, 95%CI: 1.01～1.08, P = 0.009）, and a decreased IFN-γ/IL-10 ratio （OR = 0.54, 95%CI: 0.34～0.85, P = 0.008） were independently associated with recurrence. Multivariate Cox analysis showed that elevated sTIM-3 （HR = 1.04, 95%CI: 1.01～1.07, P = 0.003） and an elevated IFN-γ/IL-10 ratio （HR = 0.55, 95%CI: 0.36～0.84, P = 0.007） remained independently associated with RFS. Further analysis of dynamic markers at 1 month postoperatively demonstrated that elevated sTIM-3 and a decreased IFN-γ/IL-10 ratio were associated with poorer RFS. Conclusions Persistent elevation of sTIM-3 and a decreased IFN-γ/IL-10 ratio after radiofrequency ablation indicate an immunosuppressive or exhaustion-dominant state, which are independently associated with an increased risk of postoperative recurrence and poorer RFS in patients with solitary colorectal cancer liver metastases. Multipoint immune monitoring combined with clinical factors such as tumor burden and ablation margin may be used for postoperative risk stratification and follow-up management.
- Colorectal liver metastasis,
- Radiofrequency ablation,
- Soluble TIM-3,
- IFN-γ/IL-10 ratio,
- Recurrence-free survival

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References(25)

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