1. Circulating microRNAs associated with prolonged overall survival in lung cancer patients treated with nivolumab.
- Author
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Halvorsen, Ann Rita, Sandhu, Vandana, Sprauten, Mette, Flote, Vidar G., Kure, Elin H., Brustugun, Odd Terje, and Helland, Åslaug
- Subjects
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LUNG cancer treatment , *THERAPEUTIC use of monoclonal antibodies , *BIOMARKERS , *CANCER patient psychology , *IMMUNOTHERAPY , *POLYMERASE chain reaction , *SURVIVAL , *MULTIPLE regression analysis , *GENE expression profiling , *MICRORNA , *DESCRIPTIVE statistics , *SEQUENCE analysis - Abstract
Background: The introduction of immune check-point inhibition in non-small cell lung cancer (NSCLC) therapy represents improved prospects for the patients. The response rates to check-point inhibitors are approximately 20% in unselected NSCLC patients. Increasing levels of tumor PD-L1 expression are associated with higher response rates. However, patients with low PD-L1 levels may also have durable responses, and improved strategies for patient stratification are needed. Material and methods: In this study, we investigated circulating microRNAs aiming to identify circulating predictive biomarkers associated with increased overall survival after immune check-point treatment. Using next generation sequencing, we performed microRNA profiling in serum from NSCLC patients (n¼20) treated with nivolumab. Serum samples from 31 patients were used for validation using qPCR assays. Serum samples were collected prior to immune therapy initiation. Results: Based on multivariate regression analysis, we identified a signature of seven microRNAs (miR- 215-5p, miR-411-3p, miR-493-5p, miR-494-3p, miR-495-3p, miR-548j-5p and miR-93-3p) significantly associated with overall survival (OS)>6 months in discovery cohort (p¼ = .0003). We further validated this in another similar set of samples (n¼31) and the model was significantly associated with overall survival (OS)>6 months (p¼ = .001) with sensitivity and specificity of 71% and 90%, respectively. Conclusions: In this study of circulating microRNAs, we have identified a 7-miR signature associated with survival in nivolumab-treated NSCLC patients. This signature may lead to better treatment options for patients with NSCLC, but a validation in an independent cohort is needed to confirm the predicted potential. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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