Abstract 21P
Background
Non-small cell lung cancer (NSCLC) is the primary cause of cancer-related death. About 20% of cases are diagnosed at an early stage, allowing an effective pulmonary resection but many patients experience disease recurrence. Biomarkers able to identify patients with a higher risk of relapse could be very useful. Circulating microRNAs (miRNAs), in both extracellular vesicles (EV)-free and EV-encapsulated forms, represent promising markers in this setting.
Methods
This is a prospective observational cohort study on early stage (IA-IIIA) NSCLC patients undergoing surgery at 3 different centers (IRST-IRCCS, VHIO and CHU de Strasburg). The main end-point was relapse within 2 years from surgery. A peripheral blood sample for plasma collection was taken from each patient pre-surgery. Circulating free and EV-derived miRNAs were extracted from plasma. MiRNA-specific libraries were prepared with the QIAseq miRNA Library Kit and sequenced on Illumina NextSeq 550. Data were normalized and analyzed for differential expression using the edgeR R statistical software package. The TMM normalization method was used. The Benjamini-Hochberg procedure was used to adjust for multiple testing.
Results
A total of 220 patients were enrolled. Median age was 68.5 (range 43.6-84.7) years. 99 (46.5%) patients had stage IA, 38 (17.8%) had stage IB, 9 (4.2%) had stage IIA, 27 (12.7%) had stage IIB and 40 (18.8%) had stage IIIA tumors. 168 (76%) had adenocarcinoma histology, 42 (19%) squamous cell carcinoma, and 12 (5%) had other tumor histotypes. The overall relapse rate was 25%, and a relapse rates of 10.5%, 16.7%, 11.1%, 38.5% and 48.6% were obtained for stage IA, IB, IIA, IIB and IIIA, respectively. Overall, 16 and 7 EV and EV-free miRNAs, respectively, resulted differently expressed in relapsed vs non-relapsed patients. 4 miRNAs (hsa-miR-182-5p, hsa-miR-183-5p, hsa-miR-1246 and hsa-miR-196b-5p) were significantly up-regulated in relapsed patients,in both EV and EV-free comparts.
Conclusions
This preliminary analysis revealed that both free and EV-derived miRNAs seem to have a role in the identification of patients with higher risk of relapse after surgery. Complete statistical analysis is ongoing and will be completed soon.
Clinical trial identification
Editorial acknowledgement
This project was supported by the Italian Ministry of Health (IT-MoH) within ERANET TRANSCAN-2 Joint Transnational Call for Proposals 2016 (JTC 2016) on: "Minimally and non-invasive methods for early detection and/or progression of cancer" (ERP-2016-23671110).
Legal entity responsible for the study
Paola Ulivi.
Funding
Italian Ministry of Health ERP-2016-23671110.
Disclosure
All authors have declared no conflicts of interest.