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Research Article: Real-world evidence of baseline soluble CD25 as a prognostic biomarker and indicator of differential EGFR–TKI benefit in stage IV lung adenocarcinoma

Date Published: 2026-07-10

Abstract:
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. 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. 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. 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.

Introduction:
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.

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