Ann Rita Halvorsen1, Vandana Sandhu1, Mette Sprauten2, Vidar G Flote2, Elin H Kure1, Odd Terje Brustugun1,3, Åslaug Helland1,2,4. 1. a Department of Cancer Genetics , Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital , Oslo , Norway. 2. b Department of Oncology , Oslo University Hospital, The Norwegian Radium Hospital , Oslo , Norway. 3. c Section of Oncology , Drammen Hospital, Vestre Viken Hospital Trust , Drammen , Norway. 4. d Institute for Clinical Medicine, University of Oslo , Oslo , Norway.
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 (n = 20) 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 (p = .0003). We further validated this in another similar set of samples (n = 31) and the model was significantly associated with overall survival (OS) > 6 months (p = .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.
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 NSCLCpatients. Increasing levels of tumorPD-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 NSCLCpatients (n = 20) 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 (p = .0003). We further validated this in another similar set of samples (n = 31) and the model was significantly associated with overall survival (OS) > 6 months (p = .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 NSCLCpatients. 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.