WCLC 2025 - Posters & ePosters-P3.13.24 Longitudinal Plasma Proteomics Identifies Predictive Biomarkers for Anti-PD-L1 Therapy in SCLC

Pdf Summary

This study conducted a comprehensive longitudinal plasma proteomic analysis in patients with extensive-stage small-cell lung cancer (SCLC) undergoing anti-PD-L1 immunotherapy combined with chemotherapy. Using 4D-DIA mass spectrometry on plasma samples collected before and during treatment, researchers sought to identify predictive biomarkers for therapy response. Patients were classified as responders (R) or non-responders (NR) based on progression-free survival (PFS) with a six-month cutoff.<br /><br />Applying machine learning and specifically a LASSO model, the study identified three key plasma proteins—VASN, PARD3, and PTGES3—that were predictive of treatment response. Individually, these proteins showed moderate predictive power (AUC values of 0.637 to 0.703), but combined into a VPP model, they achieved a higher predictive accuracy with AUC=0.846 in the training cohort (n=42). This model's performance was externally validated in an independent cohort of 40 patients, maintaining a strong AUC of 0.832.<br /><br />Notably, the VPP model outperformed existing biomarkers such as neuron-specific enolase (NSE, AUC=0.651) and neutrophil-to-lymphocyte ratio (NLR, AUC=0.630). Patients categorized as low-risk by the VPP model had significantly higher response rates (70% vs. 20%) and longer median PFS (6.87 vs. 3.97 months; HR=0.39; P=0.005) compared to the high-risk group.<br /><br />These findings suggest that plasma proteomic profiling can dynamically capture immune-related changes and that the VPP model provides a promising biomarker tool for early prediction of chemo-immunotherapy benefit in extensive-stage SCLC. The authors recommend further validation in larger prospective studies to confirm clinical utility and help guide personalized treatment decisions for this aggressive cancer subtype where reliable predictive biomarkers are currently lacking.

Asset Subtitle

Guang-Ling Jie

Meta Tag

Speaker Guang-Ling Jie

Topic Small Cell Lung Cancer and Neuroendocrine Tumors

Keywords

small-cell lung cancer

SCLC

anti-PD-L1 immunotherapy

chemotherapy

plasma proteomics

4D-DIA mass spectrometry

VASN protein

PARD3 protein

PTGES3 protein

VPP predictive model