R.E.ST.ING

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 signature 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 early-stage 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.
Secondary:
- To analyze the role of fcDNA in relation to DFS and OS
- To analyze the association between exosomal and cell-free miRNA and fcDNA and their combinations in relation to patient outcome
Methods
Two peripheral blood samples will be collected from each patient (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
From this study we expect to study 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.