Predicting immunotherapy-related adverse events in late-stage non-small cell lung cancer with KARS G12C mutation treated with PD-1 inhibitors through combined assessment of LCP1 and ADPGK expression levels

Abstract

Objective: To evaluate the potential of leukocyte-specific protein 1 (LCP1) and adenosine diphosphate-dependent glucokinase (ADPGK) as predictive biomarkers for immunotherapy-related adverse events in late-stage non-small cell lung cancer (NSCLC) patients with the KARS G12C mutation undergoing treatment with programmed cell death protein-1 (PD-1) monoclonal antibodies.

Methods: A total of 160 late-stage NSCLC patients with the KARS G12C mutation receiving PD-1 monoclonal antibody treatment were retrospectively analyzed. LCP1 and ADPGK expression levels were assessed at both mRNA and protein levels using validated methods. Statistical analyses, including correlation analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis, were conducted to explore the association between LCP1 and ADPGK expression levels and the occurrence of immunotherapy-related adverse events.

Results: The mRNA levels of LCP1 (2.43 ± 0.72 vs. 2.14 ± 0.67, t=2.311, P=0.023) and ADPGK (2.31 ± 0.61 vs. 1.98 ± 0.59, t=3.145, P=0.002) were significantly elevated in patients with adverse reactions. Similarly, protein levels of LCP1 (1.22 ± 0.28 vs. 1.07 ± 0.25, t=3.179, P=0.002) and ADPGK (1.01 ± 0.18 vs. 0.93 ± 0.19, t=2.488, P=0.015) were higher in this group. Correlation and logistic regression analyses revealed positive correlations between LCP1 and ADPGK mRNA levels and adverse event occurrence (LCP1: rho=0.186, P=0.019, OR=1.842; ADPGK: rho=0.246, P=0.002, OR=2.549). Protein levels of LCP1 and ADPGK also correlated with immunotherapy-related adverse events (LCP1: rho=0.254, P=0.001, OR=9.554; ADPGK: rho=0.19, P=0.016, OR=10.058). The combined assessment of LCP1 and ADPGK expression showed strong predictive power for identifying patients at increased risk of adverse events during PD-1 treatment (AUC=0.808), with the validation group achieving an AUC of 0.751.

Conclusion: LCP1 and ADPGK are potential independent predictive biomarkers for immunotherapy-related adverse events in late-stage NSCLC patients with the KARS G12C mutation. Their combined assessment may offer a valuable tool for risk stratification during PD-1 monoclonal antibody treatment.

Keywords: Immunotherapy-related adverse events; KARS G12C mutation; late-stage non-small cell lung cancer.