Work

Plasma cell-free RNA ITGB3 is associated with long-term clinical benefit in patients with non-small cell lung cancer receiving immunochemotherapy

Year: 2026

Type: article

Abstract: Background Predicting sustained clinical benefit from immunochemotherapy in advanced non-small cell lung cancer (NSCLC) remains a major challenge. This study aimed to identify plasma cell-free RNA (cfRNA) biomarkers for predicting long-term progression-free survival (PFS ≥24 months).Methods Extracellular vesicle-enriched cfRNA sequencing was performed on 165 patients with advanced NSCLC (discovery cohort, n=82; prospective validation cohort, n=83) and 50 healthy controls. A multistep screening approach, including differential expression and Cox regression analyses, was used to identify candidate biomarkers, which were further validated by reverse-transcription quantitative PCR.Results ITGB3 was identified as the most robust prognostic biomarker. Low baseline ITGB3 expression was significantly associated with superior survival outcomes. In the discovery cohort, the median PFS was 25.8 months for the ITGB3-low group versus 8.4 months for the ITGB3-high group (HR 0.325, p<0.0001), a result consistently observed in the validation cohort (24.9 versus 8.3 months, HR=0.42, p<0.01). ITGB3 demonstrated high prognostic accuracy with areas under the curve (AUCs) of 0.760 and 0.796 in the discovery and validation cohorts, respectively. Combining ITGB3 with three-level programmed death-ligand 1 (PD-L1) status yielded an AUC of 0.812, suggesting that the two biomarkers may provide complementary prognostic information. Multivariable analysis confirmed baseline ITGB3 as an independent prognostic factor for both PFS (HR=1.27, p<0.001) and overall survival (HR 1.31, p=0.002). Computational deconvolution suggested that the ITGB3-low cohort was characterized by a higher inferred immune-derived cfRNA fraction (70.1% vs 60.4%), particularly from monocytes and mucosal-associated invariant T cells.Conclusion Plasma cfRNA ITGB3 is a robust, non-invasive biomarker for identifying patients likely to achieve long-term benefit from immunochemotherapy, providing complementary value to traditional PD-L1 assessment.

Source: Journal for ImmunoTherapy of Cancer

DOI: 10.1136/jitc-2026-015873