WCLC 2025 - Posters & ePosters-P2.06.91 Plasma Proteomic Profiling Identifies DHX9 as a Predictive Biomarker for Chemoimmunotherapy Efficacy in Extensive-Stage Small Cell Lung Cancer

P2.06.91 Plasma Proteomic Profiling Identifies DHX9 as a Predictive Biomarker for Chemoimmunotherapy Efficacy in Extensive-Stage Small Cell Lung Cancer

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This study investigates plasma protein biomarkers predictive of chemoimmunotherapy efficacy in patients with extensive-stage small-cell lung cancer (ES-SCLC). Despite advancements in treatment, reliable biomarkers for identifying patients who benefit most from chemoimmunotherapy remain lacking. The researchers conducted proteomic profiling and identified 413 differentially expressed proteins between primary responders (PriR) and secondary responders (SecR). Functional enrichment analysis revealed upregulation of pathways related to tumor necrosis factor response and chemokine signaling in secondary responders.<br /><br />Among the proteins, ATP-dependent RNA helicase A (DHX9) and Rho GTPase-activating protein 4 (ARHGAP4) were validated in both internal (IVC) and external validation cohorts (EVC). A multivariate Cox regression model was created with these proteins, yielding a risk score (RS) to predict treatment outcomes. DHX9 showed the highest predictive performance, with an area under the curve (AUC) of 0.976 in the IVC, surpassing ARHGAP4 and RS. Using an optimal DHX9 threshold, patients were classified into DHX9-high (DHX9-H) and DHX9-low (DHX9-L) groups. The DHX9-H group exhibited significantly longer median progression-free survival (mPFS) than the DHX9-L group (10.7 vs. 2.7 months, P < 0.001). Similar results were found in the EVC, where DHX9 and RS achieved an AUC of 0.799, and the DHX9-H group again had longer mPFS compared to the DHX9-L group (7.4 vs. 4.8 months, P < 0.001).<br /><br />In summary, DHX9 emerges as a promising plasma biomarker to predict chemoimmunotherapy efficacy in ES-SCLC. Further research is needed to refine the predictive threshold using ELISA assays and validate DHX9’s clinical application. This work could help personalize treatment strategies and improve outcomes for ES-SCLC patients.

Asset Subtitle

Lina Chen

Meta Tag

Speaker Lina Chen

Topic Pathology and Biomarkers

Keywords

plasma protein biomarkers

chemoimmunotherapy efficacy

extensive-stage small-cell lung cancer

proteomic profiling

ATP-dependent RNA helicase A (DHX9)

Rho GTPase-activating protein 4 (ARHGAP4)

multivariate Cox regression model

risk score prediction

progression-free survival

tumor necrosis factor and chemokine signaling pathways