Title: Non-invasive prognostic markers for Resected Early-STage NSCLC: role of circulatING and exosomal miRNAs and free circulating DNA

Project Coordinator:
Paola ULIVI (Italy) IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRST, Meldola

Project Partners:
Enriqueta FELIP (Spain) Vall d'Hebron Institute of Oncology, Barcelona
Elisabeth QUOIX (France) CHU de Strasbourg - Hôpital Civil, Strasbourg

Project Abstract:
Background and rationale: Non-small cell lung cancer (NSCLC) is the primary cause of cancer-related death. Worldwide, about 20% of cases are diagnosed at an early stage, allowing an effective pulmonary resection. However, lung cancer 5-years survival rate remains below 16% mainly because of disseminated disease, also in fully resected early stages. Biomarkers able to identify patients with a higher risk of relapse could be very useful. Circulating microRNAs (miRNAs), in both exosome-free and exosome-encapsulated forms, represent promising markers in this setting. Some studies in the literature and our preliminary data have shown that specific miRNA signatures could have a prognostic role in NSCLC, both in the early-stage and in the metastatic disease. Moreover, free circulating DNA (fcDNA) is another prognostic marker in advanced NSCLC, whereas its role in earlystage lung cancer is not so clear yet.
Hypothesis: We hypothesize that exosomal and/or circulating miRNAs could represent prognostic biomarkers in resected-early-stage NSCLC and that a different expression profile at baseline, before surgery, could be indicative of a different patient survival. We also hypothesize that fcDNA could also be, singly or in combination with exosomal/circulating miRNAs, a prognostic biomarker in this setting.
Aims: Primary:
- To evaluate the prognostic value of exosomal and cell-free miRNAs in relation to disease free survival (DFS) and overall survival (OS) in a prospective case series of resected early-stage (stages IA-IIIA) NSCLC patients.
- To analyze the role of fcDNA in relation to DFS and OS
- To analyze the association between exosomal and cell-free miRNAs and fcDNA and their combinations in relation to patient outcome
Methods: Two peripheral blood samples will be collected from each of the 220 expected patients (stage IA-IIIA), before the surgical resection. Circulating miRNAs will be extracted from serum using specific kits. Isolation of plasma exosomes and exosome-associated miRNA extraction will be performed using specific commercial kits. Free circulating DNA will be extracted from plasma and quantified by a Real Time PCR method.
Expected results and potential impact:
We expect to evaluate the prognostic role of exosomal and cell-free miRNA and fcDNA for resected early-stage NSCLC patients. We will study these markers singly or in combination, for their capacity to predict patients with a high risk of relapse and poor survival with respect to those with a better prognosis. The use of non-invasive biomarkers in this setting could be very useful in the clinical practice for a better patient management.



(Project funded under JTC 2016)