Immunotherapy has become important treatment option for advanced NSCLC patients. Although many predictive biomarkers of immunotherapy are under exploring, such as PD-L1 expression level, tumor mutation burden, microsatellite instability and mismatch repair-deficient, they cannot fully meet the clinical demand, resulting in an urgent need for identifying novel biomarkers. Here, we explored the possibility of using plasma exosomal microRNAs as potential biomarkers for the optimal selection of advanced NSCLC patients to immunotherapy.
Plasma samples of 9 EGFR/ALK-wild type (WT) (confirmed by ARMS and IHC method) advanced NSCLC patients were collected before the administration of PD-1/PD-L1 inhibitors. The efficacy evaluation was conducted after 3 cycles of the treatment. Post-treatment plasmas were collected from 4 disease control (DC) patients (PR and SD). Plasma from 7 healthy individuals was collected as control. Exosomes were extracted by ultracentrifugation and exosomal miRNAs were analyzed by small RNA next-generation sequencing.
Cancer patients' exosomal miRNA profiles can be distinguished from those in healthy individuals by PCA clustering, which post-treatment samples also tend to separate from pre-treatment samples. A total of 120 exosomal miRNAs were differentially presented in advanced NSCLCs compared to healthy individuals (FDR<0.01, p < 0.05 by exact test). Three miRNAs (miR-320d, miR-320c, miR-320b) from the miR320 family were identified differentially up-regulated in PD groups compared to DC patients and healthy individuals. In addition, we identified 311 differentially expressed exosomal miRNAs (111 up and 200 down-regulated) in post-treatment samples compared to pre-treatment samples, including down-regulated miR-125b-5p (a γβ T cell suppressor), miR-1246 and miR-1290, as well as up-regulated miR-4433b and miR-744-5p. Based on the results, these miRNAs may serve as predictive biomarkers for immunotherapy.
Cancer patients' exosomal miRNA profile differs from healthy individuals. The baseline profile of plasma exosomal microRNAs and its dynamic change might be correlative with the efficacy of immunotherapy in EGFR/ALK wild type advanced NSCLC.
Clinical trial identification
Legal entity responsible for the study
Guangdong Lung Cancer Institute.
Has not received any funding.
R. Yu, X. Wu: Employee: Geneseeq Technology Inc. Y.W. Shao: Shareholder: Geneseeq Technology Inc. All other authors have declared no conflicts of interest.