Abstract 5823
Background
In resected non-small cell lung cancer (NSCLC) considerable recurrence rates has been reported (30%). Tumor secretes small extracellular vesicles known as exosomes, which plays a role in the metastasis process. Pulmonary tumor-draining vein blood has proved to be better source than peripheral vein to analyze the prognosis impact of exosomes (Navarro A, et al. Cancers 2019). LincRNA-p21 is a long non-coding RNA which upregulation in tumor tissue induced by hypoxia was related to poor prognosis in NSCLC (Castellano JJ. et al. JTO 2016). We aimed to evaluate the presence of lincRNA-p21 in exosomes and its potential as prognosis biomarker in resected NSCLC patients.
Methods
H23 and H1299 NSCLC cell lines were cultured in exosome-free medium 48h under normoxic/hypoxic conditions. LincRNA-p21 was inhibited using a siRNA and quantified using a TaqMan assay. Exosomes were purified by ultracentrifugation and characterized by electron microscopy, western blot and Nanosight. LincRNA-p21 was analyzed in exosomes from pulmonary tumor-draining vein, obtained during surgery, from 54 NSCLC patients.
Results
LincRNA-p21 was present in exosomes showing 18 times more representation than in their origin cells. Under hypoxic conditions exosomal lincRNA-p21 was upregulated in both cell lines (p < 0.05). Cellular lincRNA-p21 silencing resulted in a reduction in exosomal lincRNA-p21 (p = 0.04) indicating a relation between cellular and exosomal levels. The analysis in patient samples showed that lincRNA-p21 was present in patient exosomes obtained from tumor-draining vein. The survival analysis showed that high exosomal lincRNA-p21 levels were associated with shorter time to relapse (TTR) (37 vs 56 months; p = 0.03) and shorter overall survival (OS) (46 vs 66 months; p = 0.04). In the multivariate analysis exosomal lincRNA-p21 emerged as an independent prognostic marker for TTR (HR: 3.1; 95%CI: 1.02-9.4; p = 0.04) and OS (HR: 5.3; 95%CI: 1.6-17.2; p = 0.006) together with disease stage.
Conclusions
Tumor exosomes carry LincRNA-p21, which increases under hypoxia, and its analysis in tumor-draining vein arises as a promising prognosis marker.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
SAF2017-88606-P (AEI/FEDER, UE).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3620 - Safety, efficacy, PK and PD biomarker results of the first-in-human study of mutant isocitrate dehydrogenase 1 (mIDH1) inhibitor BAY 1436032 in patients (pts) with mIDH1 advanced solid tumours
Presenter: Wolfgang Wick
Session: Poster Display session 1
Resources:
Abstract
5465 - Proof of concept clinical study by US-guided intratumor injection of VCN-01, an oncolytic adenovirus expressing hyaluronidase in patients with pancreatic cancer
Presenter: Manuel Hidalgo
Session: Poster Display session 1
Resources:
Abstract
2555 - A Phase 1a/b first-in-human, open-label, dose-escalation, safety, PK and PD study of TP-0903 in solid tumors
Presenter: John Sarantopoulos
Session: Poster Display session 1
Resources:
Abstract
3533 - First in human phase 1/2a study of PEN-866, a Heat Shock Protein 90 (HSP90) ligand – SN38 conjugate for patients with advanced solid tumors: Phase 1 results
Presenter: Johanna Bendell
Session: Poster Display session 1
Resources:
Abstract
4114 - A Phase I Open-Label, Non-Randomized Study of Recombinant Super-Compound Interferon (rSIFN-co) In Patients with Advanced Solid Tumors
Presenter: Amanda Seet
Session: Poster Display session 1
Resources:
Abstract
2537 - Evaluation of Pharmacodynamic (PD) Biomarkers in Advanced Cancer Patients Treated with Oxidative Phosphorylation (OXPHOS) Inhibitor, OPC-317 (OPC)
Presenter: Jie Qing Eu
Session: Poster Display session 1
Resources:
Abstract
5764 - Pharmacokinetic (PK) assessment of BT1718: A phase 1/2a study of BT1718, a first in class Bicycle Toxin Conjugate (BTC), in patients (pts) with advanced solid tumours
Presenter: Natalie Cook
Session: Poster Display session 1
Resources:
Abstract
2683 - A phase I open label dose escalation trial evaluating VT1021 in patients with advanced solid tumors.
Presenter: Wael Harb
Session: Poster Display session 1
Resources:
Abstract
3609 - Interim Results from Trial of SL-801, a Novel XPO-1 Inhibitor, in Patients with Advanced Solid Tumors
Presenter: Judy Wang
Session: Poster Display session 1
Resources:
Abstract
3485 - Phase 1 Trial of Fruquintinib in Patients with Advanced Solid Tumors: Results of the Dose Escalation Phase
Presenter: Andrea Wang-Gillam
Session: Poster Display session 1
Resources:
Abstract