Frontiers in oncology · 2026
Real-world evidence of baseline soluble CD25 as a prognostic biomarker and indicator of differential EGFR-TKI benefit in stage IV lung adenocarcinoma.
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Guo Huiru, Liu Lingshuang, Lindberg Veronika, Xue Yingjun, Baak Jan P A
Аннотация
BACKGROUND: Outcomes in stage IV lung adenocarcinoma (LUAD) remain heterogeneous despite established genomic and immune biomarkers. We evaluated the prognostic and predictive value of soluble interleukin-2 receptor (sCD25), a marker of systemic inflammation and immune regulation.
METHODS: In this prospective observational real-world study (2020-2024), 133 consecutive patients with newly diagnosed stage IV LUAD, ECOG performance status 0-1, and survival ≥3 months were enrolled. Overall survival (OS) was the primary endpoint. Associations between sCD25 and OS were assessed using Kaplan-Meier estimates, multivariable Cox regression, and propensity score matching. Treatment-by-biomarker interaction analyses evaluated EGFR tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and antiangiogenic therapy.
RESULTS: In the whole group, at a median follow-up of 24.1 months, 52 deaths occurred during follow-up. Elevated sCD25 (≥441 U/mL) was associated with shorter OS (hazard ratio [HR], 5.70; 95% CI, 2.94-11.07; P <.0001) and remained prognostic in multivariable analysis (HR, 4.23; 95% CI, 2.01-8.91; P <.001) and after propensity score matching (HR, 4.61; 95% CI, 2.01-10.62; P <.001). One- and three-year OS rates were 97% and 78% for low sCD25 versus 68% and 27% for high sCD25. A significant treatment interaction was observed for EGFR-TKIs, with benefit limited to the high-sCD25 subgroup (HR, 0.41; 95% CI, 0.19-0.88; P = .02). No significant interactions were observed for ICIs or antiangiogenic therapy.
CONCLUSION: Baseline sCD25 is a biomarker in stage IV LUAD -strongly prognostic and suggests differential benefit from EGFR-TKIs-and may help refine EGFR-TKI selection. Multicenter validation is warranted.
METHODS: In this prospective observational real-world study (2020-2024), 133 consecutive patients with newly diagnosed stage IV LUAD, ECOG performance status 0-1, and survival ≥3 months were enrolled. Overall survival (OS) was the primary endpoint. Associations between sCD25 and OS were assessed using Kaplan-Meier estimates, multivariable Cox regression, and propensity score matching. Treatment-by-biomarker interaction analyses evaluated EGFR tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and antiangiogenic therapy.
RESULTS: In the whole group, at a median follow-up of 24.1 months, 52 deaths occurred during follow-up. Elevated sCD25 (≥441 U/mL) was associated with shorter OS (hazard ratio [HR], 5.70; 95% CI, 2.94-11.07; P <.0001) and remained prognostic in multivariable analysis (HR, 4.23; 95% CI, 2.01-8.91; P <.001) and after propensity score matching (HR, 4.61; 95% CI, 2.01-10.62; P <.001). One- and three-year OS rates were 97% and 78% for low sCD25 versus 68% and 27% for high sCD25. A significant treatment interaction was observed for EGFR-TKIs, with benefit limited to the high-sCD25 subgroup (HR, 0.41; 95% CI, 0.19-0.88; P = .02). No significant interactions were observed for ICIs or antiangiogenic therapy.
CONCLUSION: Baseline sCD25 is a biomarker in stage IV LUAD -strongly prognostic and suggests differential benefit from EGFR-TKIs-and may help refine EGFR-TKI selection. Multicenter validation is warranted.