Monitoring HOTTIP levels on extracellular vesicles for predicting recurrence in surgical non-small cell lung cancer patients

• Published in: Translational oncology 2021-08, Vol.14 (8), p.101144-101144, Article 101144
• Main Authors: Han, Bing, Marrades, Ramón María, Viñolas, Nuria, He, Yangyi, Canals, Jordi, Díaz, Tania, Molins, Laureano, Martinez, Daniel, Moisés, Jorge, Sánchez, David, Boada, Marc, Acosta-Plasencia, Melissa, Cros-Font, Coralí, Monzo, Mariano, Navarro, Alfons
• Format: Article
• Language: English
• Subjects: Extracellular vesicles; HOTTIP; liquid biopsy; lncRNA; NSCLC; Original Research
• ISSN: 1936-5233; 1936-5233
• DOI: 10.1016/j.tranon.2021.101144

•EV HOTTIP analysis during post-surgical follow-up allows early recurrence detection.•Detection of an increment of EV HOTTIP level in first post-surgical sample predicts recurrence with a sensitivity of 87.5% and specificity of 90.9%.•Detection of an increment of EV HOTTIP level in first post-surgical sample predicts worse patient outcome.•EV HOTTIP could be considered as a follow-up biomarker for monitoring recurrence in NSCLC. In resected non-small cell lung cancer (NSCLC), postsurgical recurrence is the major factor affecting long-term survival. The identification of biomarkers in extracellular vesicles (EV) obtained from serial blood samples after surgery could enhance early detection of relapse and improve NSCLC outcome. Since EV cargo contains long non-coding RNAs (lncRNAs), we aimed to analyze whether the oncogenic lncRNA HOTTIP, which higher expression in tumor tissue was related to worse outcome in NSCLC, could be detected in EV from NSCLC patients and serve as recurrence biomarker. After purification of EVs by ultracentrifugation in 52 serial samples from 18 NSCLC patients, RNA was isolated and HOTTIP was quantified by Real time PCR. We observed that patients that relapsed after surgery displayed increased postsurgical EV HOTTIP levels in comparison with presurgical levels. In the relapsed patients with several samples available between surgery and relapse, we observed an increment in the EV HOTTIP levels when approaching to relapse, which indicated its potential utility for monitoring disease recurrence. When we focused in EV HOTTIP levels in the first post-surgical sample, we observed that the detection of an increment of the expression levels in comparison to presurgical sample, predicted recurrence with high sensitivity (85.7%) and specificity (90.9%) and that patients had shorter time to relapse and shorter overall survival. In conclusion, our pilot study showed that EV HOTTIP is a potential biomarker for monitoring disease recurrence after surgery in NSCLC.