Abstract 1156P
Background
Potential curative surgery is the preferential therapeutic option for early-stage non-small cell lung cancer (NSCLC). The outcome of these patients it is still very unfavorable, and it is believed that early detection and treatment of recurrence could improve their survival. Patient surveillance after surgery is mostly based in imaging techniques and few circulating biomarkers have been identified. Long non-coding RNAs (lncRNAs) and their analysis in exosomes have recently emerged as promising blood-based biomarkers. LncRNA HOTTIP has been previously identified as prognostic biomarker in early-stage NSCLC by our group. Now, we aimed to evaluate the potential role of the exosomal HOTTIP as a longitudinal plasma-based assessment for early detection of post-surgical recurrence.
Methods
Exosomal HOTTIP has been analyzed in 52 longitudinal samples from 18 resected NSCLC patients. Mean patient age was 65 years (39-83); 28% were stage I; and eleven patients received adjuvant treatment after surgery. Longitudinal samples were obtained before and during routine follow up visits after surgery. Exosomes from plasma were obtained by ultracentrifugation and HOTTIP was quantified by qRT-PCR.
Results
After a median follow-up of 55 months (IQR:53-65) seven patients (39%) relapsed and six of them died by the disease. In relapsed patients, exosomal HOTTIP levels gradually increment from surgery to clinical diagnosis of relapse. Interestingly, we observed that comparing only pre-surgical and first post-surgical sample we were able to predict relapse with high sensitivity (85.7%) and specificity (90.9%), with an area under the curve value of 0.935 (95% CI: 0.819–1.0; p=0.002). When we divided patients in two groups depending on whether exosomal HOTTIP levels increased or not in the first postsurgical sample, we observed that patients with increased levels after surgery had shorter time to relapse (9.7 months vs not reached; p=0.001) and shorter overall survival (13.1 months vs not reached; p=0.012) than patients that had no change or reduced their levels.
Conclusions
This pilot study shows that exosomal HOTTIP could be a potential surveillance biomarker for prediction of postoperative recurrence in NSCLC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Molecular Oncology and Embryology Laboratory, Human Anatomy Unit, Faculty of Medicine and Health Sciences, University of Barcelona.
Funding
The Ministry of Economy, Industry, and Competition, Agencia Estatal de Investigación co-financed with the European Union FEDER funds SAF2017-88606-P (AEI/FEDER, UE).
Disclosure
All authors have declared no conflicts of interest.