Simple Summary Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC) leading to substantial improvement in survival time and quality of life. Nevertheless, the clinical benefit of treatment is still limited to a minority of patients, reflecting the need to identify novel noninvasive biomarkers to improve patient selection. Currently available markers such as PD-L1 expression have important limitations. In this study, we focused on extracellular vesicles (EV)-associated miRNAs produced by cancer cells and their microenvironment that can be easily detected in blood. In particular, after a large-scale screening of 799 EV-miRNAs, we identified EV-miR-625-5p as a novel independent biomarker of response and survival in ICI-treated NSCLC patients, in particular in patients with PD-L1 expression >= 50%. EV-miR-625-5p integrated with PDL-1 test could allow the clinician to identify in advance patients that would benefit from ICIs. Immune checkpoint inhibitors (ICIs) are largely used in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). Novel biomarkers that provide biological information that could be useful for clinical management are needed. In this respect, extracellular vesicles (EV)-associated microRNAs (miRNAs) that are the principal vehicle of intercellular communication may be important sources of biomarkers. We analyzed the levels of 799 EV-miRNAs in the pretreatment plasma of 88 advanced NSCLC patients who received anti-PD-1 therapy as single agent. After data normalization, we used a two-step approach to identify candidate biomarkers associated to both objective response (OR) by RECIST and longer overall survival (OS). Univariate and multivariate analyses including known clinicopathologic variables and new findings were performed. In our cohort, 24/88 (27.3%) patients showed OR by RECIST. Median OS in the whole cohort was 11.5 months. In total, 196 EV-miRNAs out 799 were selected as expressed above background. After multiplicity adjustment, abundance of EV-miR-625-5p was found to be correlated with PD-L1 expression and significantly associated to OR by RECIST (p = 0.0366) and OS (p = 0.0031). In multivariate analysis, PD-L1 staining and EV-miR-625-5p levels were constantly associated to OR and OS. Finally, we showed that EV-miR-625-5p levels could discriminate patients with longer survival, in particular in the class expressing PD-L1 >= 50%. EV-miRNAs represent a source of relevant biomarkers. EV-miR-625-5p is an independent biomarker of response and survival in ICI-treated NSCLC patients, in particular in patients with PD-L1 expression >= 50%.

Pantano, F., Zalfa, F., Iuliani, M., Simonetti, S., Manca, P., Napolitano, A., et al. (2022). Large−Scale Profiling of Extracellular Vesicles Identified miR−625−5p as a Novel Biomarker of Immunotherapy Response in Advanced Non−Small−Cell Lung Cancer Patients. CANCERS, 14(10), 2435 [10.3390/cancers14102435].

Large−Scale Profiling of Extracellular Vesicles Identified miR−625−5p as a Novel Biomarker of Immunotherapy Response in Advanced Non−Small−Cell Lung Cancer Patients

Vulpis E.;Bei R.;
2022-01-01

Abstract

Simple Summary Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC) leading to substantial improvement in survival time and quality of life. Nevertheless, the clinical benefit of treatment is still limited to a minority of patients, reflecting the need to identify novel noninvasive biomarkers to improve patient selection. Currently available markers such as PD-L1 expression have important limitations. In this study, we focused on extracellular vesicles (EV)-associated miRNAs produced by cancer cells and their microenvironment that can be easily detected in blood. In particular, after a large-scale screening of 799 EV-miRNAs, we identified EV-miR-625-5p as a novel independent biomarker of response and survival in ICI-treated NSCLC patients, in particular in patients with PD-L1 expression >= 50%. EV-miR-625-5p integrated with PDL-1 test could allow the clinician to identify in advance patients that would benefit from ICIs. Immune checkpoint inhibitors (ICIs) are largely used in the treatment of patients with advanced non-small-cell lung cancer (NSCLC). Novel biomarkers that provide biological information that could be useful for clinical management are needed. In this respect, extracellular vesicles (EV)-associated microRNAs (miRNAs) that are the principal vehicle of intercellular communication may be important sources of biomarkers. We analyzed the levels of 799 EV-miRNAs in the pretreatment plasma of 88 advanced NSCLC patients who received anti-PD-1 therapy as single agent. After data normalization, we used a two-step approach to identify candidate biomarkers associated to both objective response (OR) by RECIST and longer overall survival (OS). Univariate and multivariate analyses including known clinicopathologic variables and new findings were performed. In our cohort, 24/88 (27.3%) patients showed OR by RECIST. Median OS in the whole cohort was 11.5 months. In total, 196 EV-miRNAs out 799 were selected as expressed above background. After multiplicity adjustment, abundance of EV-miR-625-5p was found to be correlated with PD-L1 expression and significantly associated to OR by RECIST (p = 0.0366) and OS (p = 0.0031). In multivariate analysis, PD-L1 staining and EV-miR-625-5p levels were constantly associated to OR and OS. Finally, we showed that EV-miR-625-5p levels could discriminate patients with longer survival, in particular in the class expressing PD-L1 >= 50%. EV-miRNAs represent a source of relevant biomarkers. EV-miR-625-5p is an independent biomarker of response and survival in ICI-treated NSCLC patients, in particular in patients with PD-L1 expression >= 50%.
2022
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/04 - PATOLOGIA GENERALE
English
Con Impact Factor ISI
immune checkpoint inhibitors
non-small-cell lung cancer
extracellular vesicles
microRNAs
Pantano, F., Zalfa, F., Iuliani, M., Simonetti, S., Manca, P., Napolitano, A., et al. (2022). Large−Scale Profiling of Extracellular Vesicles Identified miR−625−5p as a Novel Biomarker of Immunotherapy Response in Advanced Non−Small−Cell Lung Cancer Patients. CANCERS, 14(10), 2435 [10.3390/cancers14102435].
Pantano, F; Zalfa, F; Iuliani, M; Simonetti, S; Manca, P; Napolitano, A; Tiberi, S; Russano, M; Citarella, F; Foderaro, S; Vulpis, E; Zingoni, A; Masuelli, L; Bei, R; Ribelli, G; Del Re, M; Danesi, R; Vincenzi, B; Perrone, G; Tonini, G; Santini, D
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/302009
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