Lung cancer (Amsterdam, Netherlands) · 2025
Identification of poor prognostic factors using circulating extracellular vesicles in durvalumab consolidation therapy for locally advanced non-small cell lung cancer.
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Utsumi Hirofumi, Yagishita Shigehiro, Kawajiri Kazuki, Torasawa Masahiro, Kiritani Ayu, Tamura Kentaro, Wakui Hiroshi, Horinouchi Hidehito, Araya Jun, Fujita Yu
Аннотация
BACKGROUND: The risk factors associated with treatment resistance to consolidation durvalumab following chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (NSCLC) have not been well established.
METHODS: Extracellular vesicles (EVs) were isolated from the pretreatment serum of 73 patients treated with consolidation durvalumab. Isolation was performed using CD9/CD63 antibodies, and EV proteins were identified using liquid chromatography-tandem mass spectrometry (LC-MS). The relationship between the expression of these proteins and progression-free survival (PFS) after durvalumab initiation was analyzed.
RESULTS: The median PFS was not reached(NR) (95 % confidence interval [CI], 17.2 months-NR), andthe 24-month PFS rate was 54.7 % (95 % CI, 44.4-67.4). Proteomic analysis of circulating EVs identified RPS27A, SAA1, and S100A7 as the primary candidate biomarkers. Notably, patients with high RPS27A expression exhibited a significantly shorter PFS compared with those with low expression; hazard ratio (HR) 2.93 (95 % CI: 1.48-5.79),P = 0.002. Similarly, high SAA1 expression was associated with a shorter PFS; HR 2.94 (95 % CI: 1.37-6.30), P = 0.006. High S100A7 expression also correlated with poorer outcomes; HR 2.94 (95 % CI: 1.43-6.04), P = 0.003. In multivariate analysis, a high expression level of RPS27A was identified as an independent predictor of poor PFS; HR 2.29 (95 % CI: 1.01-5.17), P = 0.047. Multivariate receiver operating characteristic (ROC) analysis incorporating these three proteins yielded an area under the curve (AUC) of 0.71 (95 % CI: 0.59-0.83).
CONCLUSION: This study demonstratedfavorable PFS outcomes in patients receiving durvalumab consolidation therapy. Circulating EV proteomic analysis identified RPS27A, SAA1, and S100A7, particularly RPS27A, as potential biomarkers for predicting resistance to durvalumab.
METHODS: Extracellular vesicles (EVs) were isolated from the pretreatment serum of 73 patients treated with consolidation durvalumab. Isolation was performed using CD9/CD63 antibodies, and EV proteins were identified using liquid chromatography-tandem mass spectrometry (LC-MS). The relationship between the expression of these proteins and progression-free survival (PFS) after durvalumab initiation was analyzed.
RESULTS: The median PFS was not reached(NR) (95 % confidence interval [CI], 17.2 months-NR), andthe 24-month PFS rate was 54.7 % (95 % CI, 44.4-67.4). Proteomic analysis of circulating EVs identified RPS27A, SAA1, and S100A7 as the primary candidate biomarkers. Notably, patients with high RPS27A expression exhibited a significantly shorter PFS compared with those with low expression; hazard ratio (HR) 2.93 (95 % CI: 1.48-5.79),P = 0.002. Similarly, high SAA1 expression was associated with a shorter PFS; HR 2.94 (95 % CI: 1.37-6.30), P = 0.006. High S100A7 expression also correlated with poorer outcomes; HR 2.94 (95 % CI: 1.43-6.04), P = 0.003. In multivariate analysis, a high expression level of RPS27A was identified as an independent predictor of poor PFS; HR 2.29 (95 % CI: 1.01-5.17), P = 0.047. Multivariate receiver operating characteristic (ROC) analysis incorporating these three proteins yielded an area under the curve (AUC) of 0.71 (95 % CI: 0.59-0.83).
CONCLUSION: This study demonstratedfavorable PFS outcomes in patients receiving durvalumab consolidation therapy. Circulating EV proteomic analysis identified RPS27A, SAA1, and S100A7, particularly RPS27A, as potential biomarkers for predicting resistance to durvalumab.