Abstract 1216P
Background
Currently, predictive factors for recurrence risk of resected, early stage non-small cell lung cancer (NSCLC) are limited to post-surgical stage, and novel predictors might improve patient selection for adjuvant chemotherapy. Recently, circulating tumor-derived exosome (Exo) miRNAs have emerged as highly specific non-invasive biomarkers for early NSCLC diagnosis. In this study, we aimed at identifying an Exo-miRNA signature to select resected NSCLC patients at higher risk of disease recurrence.
Methods
The expression profiles of 2,549 miRNAs were screened by microarray in the plasma Exo-miRNome isolated from 67 patients, who underwent resection for NSCLC and had a follow-up of at least 5 years. The plasma for Exo-miRNome analysis was collected before surgery. To build a predictive score, we applied penalized Cox regression analysis, with the LASSO method, to a subset of miRNAs with mean logIntensity higher than 5, age, sex and stage. Finally, we plotted the Kaplan-Meier curves of patients divided according to the median predictive score and tested their difference using the Log Rank test.
Results
The median age of patients was 68 years, of whom 76% were men. The disease stages were classified as follows: stage I (42%), stage II (46%), stage III (12%). Disease recurrence (interval: 4-75 months) was observed in 36/67 (54%) patients. A patient “risk score” was built by combining the stage with 5 (miR-4481, miR-4436b-3p, let-7b-3p, let-7e-5p, miR-3620-3p) and 3 (miR-4716-5p, miR-1249-3p, miR-6766-3p) Exo-miRNAs, which were either positively or negatively associated with disease recurrence, respectively. Differences of both recurrence-free survival and overall survival of patients’ groups were statistically significant (p<0.0001 for both) according to the predictive risk score. In particular, high risk patients had median recurrence-free survival 4 times lower than low risk patients.
Conclusions
We identified a score, based on 8 Exo-miRNAs and disease stage, which resulted able to predict the risk relapse after surgery for early stage NSCLC. High-risk patients may thus be eligible for personalized protocols involving post-operative chemotherapy or radiotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Genova: Honoraria (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self): Boehringer Ingelheim; Honoraria (self): MSD; Honoraria (self): Roche. All other authors have declared no conflicts of interest.