Simultaneous Investigation of SST2, IL-33, and Caspase-3 Serum Levels in Non-Small Cell Lung Cancer

Abstract

Background/Aim: Non-small cell lung cancer (NSCLC) is a type of lung cancer with a high mortality rate. Many molecular and biochemical mechanisms are involved in its development, among which the suppression of tumorigenicity-2 protein (ST2) signaling pathway. Soluble ST2 (sST2) competes with transmembrane ST2 (ST2 ligand) for IL-33 binding. Activation of IL-33/ST2 pathway leads to M2 macrophage polarization, which promotes tumor progression. Since Caspase-3 is implicated in the regulation of IL-33 activity, the present study aimed to analyze the serum levels of IL-33, sST2, and caspase-3 in non-small cell lung cancer patients, compare them with control samples, and simultaneously investigate their predictive capacity. Materials and Methods: In this study, sST2 protein, IL-33, and caspase-3 levels were investigated using the ELISA method in serum samples collected from 25 patients diagnosed with non-small cell lung cancer and 25 completely healthy volunteer individuals. In the study, receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic power of the biomarkers. Results: Serum IL-33 levels were found to be significantly elevated in patients compared to the control group (p<0.0001). Similarly, the patient group showed significantly higher caspase-3 serum levels than the control group (p<0.030). While sST2 serum levels were higher in the patient group, the difference did not reach statistical significance. The ROC analysis for IL-33 showed an area under the curve (AUC) value of 0.838 [95% confidence interval (CI)=0.725-0.952, p<0.05], indicating that IL-33 is good diagnostic capability for NSCLC. The AUC value for Caspase-3 was 0.678 (95% CI=0.525-0.832, p=0.023), while for sST2, the AUC value was 0.499 (95% CI=0.333-0.665, p>0.05). Conclusion: NSCLC patients are characterized by increased IL-33 and caspase-3 serum levels. These findings suggest that these markers could serve as valuable diagnostic and prognostic indicators, in addition to being potential therapeutic targets. © 2025 Elsevier B.V., All rights reserved.