Persistent and novel changes in plasma microRNA profiles in patients with non-small cell lung cancer following tumour resection

Background: Non-small cell lung cancer (NSCLC) accounts for 80% of lung cancers, the leading cause of cancer mortality. microRNAs (miRNA, miR) have emerged as important components of carcinogenesis and promising biomarkers. We aimed to analyse global plasma miRs in NSCLC patients before and at least one year after tumour resection. Methods: Plasma was collected from the peripheral blood of 24 donors without cancer and of NSCLC patients before surgery (n=36) and at least 1 year after surgery (n=12). Next-generation sequencing (NGS)based miR profiling was performed. Patients were followed-up for 4 to 12 years after surgery to assess disease recurrence. Results: Untreated NSCLC patients exhibited significant changes in plasma miR levels compared to cancer-free donors (48 up- and 17 down-regulated miRs). miR profiles in patients with adenocarcinoma (ADC) (n=18) and squamous cell carcinoma (SCC) significantly differed (16 and 86 miRs up-, and 15 and 16 miRs down-regulated, respectively). A subset of pre-surgery deregulated miRs was found to be associated with recurrence (49 miRs). Six miRs were shown to have independent prognostic value. After tumour resection, some pre-surgery miR alterations returned to control levels (18 miRs), some others persisted (27 miRs), while also novel plasma miR changes emerged (75 miRs) in patients with no clinical evidence of recurrence. Conclusions: Untreated NSCLC patients present deregulated plasma miRs, some of which may have a potential of prognostic markers. After tumour excision plasma miR profiles change, some miR levels normalise, some changes persist and novel miR changes are observed despite no clinical symptoms of recurrence. Plasma miR profiles in NSCLC patients may suggest systemic abnormalities predisposing to lung cancer and/or reflect a systemic response to pre-cancer/dormant cancer cells.