Pretreatment serum IRAK4 and NLRP3 concentrations, their combined score, and overall survival in non-small cell lung cancer: a retrospective single-center cohort study
4 affiliations
- 1Department of Respiratory Medicine, Qingdao University, Qingdao, China
- 2The Staff Health Care Office, Qingdao Municipal Hospital, Qingdao, China
- 3Department of Personnel and the Nursing Management Committee, Qingdao Municipal Hospital, Qingdao, China
- 4Department of Respiratory Medicine, Qingdao Municipal Hospital, Qingdao University, No. 5 Donghai Middle Road, Qingdao, 266071 China
Abstract
Objective: To evaluate the prognosticsignificance of pretreatment serum IRAK4, NLRP3, and an exploratory combined score in patients with non-small cell lung cancer (NSCLC).
Methods: This retrospective cohort study included 493 patients with histologically confirmed NSCLC treated at Qingdao Municipal Hospital between 2010 and 2019. Pretreatment serum IRAK4 and NLRP3 concentrations were measured using enzyme-linked immunosorbent assay (ELISA), and a combined score was calculated as Ln(IRAK4) + Ln(NLRP3), representing a mathematical composite of the two biomarkers and used for exploratory analysis. The primary endpoint was all-cause overall survival (OS), defined from diagnosis to death from any cause or censoring. Prognostic performance was evaluated using time-dependent receiver operating characteristic (tROC) analysis, Cox proportional hazards models with progressive adjustment, restricted cubic spline (RCS) analysis, calibration curves, and decision curve analysis (DCA).
Results: During a median follow-up of 55.3 months, 224 patients (45.4%) died. In multivariable Cox analyses, higher IRAK4, NLRP3, and combined-score values were associated with poorer OS. IRAK4 (HR = 1.65, 95% CI 1.42–1.93), NLRP3 (HR = 1.23, 95% CI 1.17–1.29), and the combined score (HR = 3.42, 95% CI 2.72–4.31) remained associated with worse survival after adjustment for available clinical covariates (all P < 0.001). At the 3-year landmark, the combined score showed higher biomarker-only discrimination than IRAK4, NLRP3, CEA, and NSE, with an AUC of 0.816. However, its incremental discrimination beyond the clinical model was limited: no improvement was observed at 1 year, no significant improvement at 2 years, and only a modest increase was observed at 3 years (AUC 0.913 vs. 0.899; P = 0.006). Calibration assessment was limited to descriptive calibration plots and calibration slope because the calibration intercept and Brier score could not be reliably estimated. Sensitivity analyses showed broadly consistent associations. No external validation was performed.
Conclusion: Higher pretreatment serum IRAK4 and NLRP3 concentrations and their exploratory combined score were associated with poorer all-cause OS in this single-center NSCLC cohort. The score showed higher internal biomarker-only discrimination, particularly at 3 years, but limited incremental discrimination beyond available clinical variables. It is not clinically validated; external validation is required before its clinical utility can be evaluated.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16605-y.
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BibTeX
@article{qiao2026pretreatment,
title = {{Pretreatment serum IRAK4 and NLRP3 concentrations, their combined score, and overall survival in non-small cell lung cancer: a retrospective single-center cohort study}},
author = {Han Qiao and Xiaolei Han and Lei Zhao and Huaping Tang},
journal = {BMC Cancer},
year = {2026},
month = aug,
doi = {10.1186/s12885-026-16605-y},
url = {https://doi.org/10.1186/s12885-026-16605-y},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Pretreatment serum IRAK4 and NLRP3 concentrations, their combined score, and overall survival in non-small cell lung cancer: a retrospective single-center cohort study
AU - Han Qiao
AU - Xiaolei Han
AU - Lei Zhao
AU - Huaping Tang
PY - 2026
DA - 2026/08/06
JO - BMC Cancer
DO - 10.1186/s12885-026-16605-y
UR - https://doi.org/10.1186/s12885-026-16605-y
AB - Objective: To evaluate the prognosticsignificance of pretreatment serum IRAK4, NLRP3, and an exploratory combined score in patients with non-small cell lung cancer (NSCLC). Methods: This retrospective cohort study included 493 patients with histologically confirmed NSCLC treated at Qingdao Municipal Hospital between 2010 and 2019. Pretreatment serum IRAK4 and NLRP3 concentrations were measured using enzyme-linked immunosorbent assay (ELISA), and a combined score was calculated as Ln(IRAK4) + Ln(NLRP3), representing a mathematical composite of the two biomarkers and used for exploratory analysis. The primary endpoint was all-cause overall survival (OS), defined from diagnosis to death from any cause or censoring. Prognostic performance was evaluated using time-dependent receiver operating characteristic (tROC) analysis, Cox proportional hazards models with progressive adjustment, restricted cubic spline (RCS) analysis, calibration curves, and decision curve analysis (DCA). Results: During a median follow-up of 55.3 months, 224 patients (45.4%) died. In multivariable Cox analyses, higher IRAK4, NLRP3, and combined-score values were associated with poorer OS. IRAK4 (HR = 1.65, 95% CI 1.42–1.93), NLRP3 (HR = 1.23, 95% CI 1.17–1.29), and the combined score (HR = 3.42, 95% CI 2.72–4.31) remained associated with worse survival after adjustment for available clinical covariates (all P < 0.001). At the 3-year landmark, the combined score showed higher biomarker-only discrimination than IRAK4, NLRP3, CEA, and NSE, with an AUC of 0.816. However, its incremental discrimination beyond the clinical model was limited: no improvement was observed at 1 year, no significant improvement at 2 years, and only a modest increase was observed at 3 years (AUC 0.913 vs. 0.899; P = 0.006). Calibration assessment was limited to descriptive calibration plots and calibration slope because the calibration intercept and Brier score could not be reliably estimated. Sensitivity analyses showed broadly consistent associations. No external validation was performed. Conclusion: Higher pretreatment serum IRAK4 and NLRP3 concentrations and their exploratory combined score were associated with poorer all-cause OS in this single-center NSCLC cohort. The score showed higher internal biomarker-only discrimination, particularly at 3 years, but limited incremental discrimination beyond available clinical variables. It is not clinically validated; external validation is required before its clinical utility can be evaluated. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16605-y.
SN - 1471-2407
ER -