Identification of specific miRNA signatures in EBC for non-invasive lung cancer diagnosis and prognosis: A proof-of-concept study

<bold>Background:</bold> Lung cancer (LC) is the leading cause of cancer-related deaths globally. MicroRNAs are powerful genetic regulators and that can be used to develop novel diagnostic tools. Exhaled breath condensate (EBC) contains miRNAs from the lower respiratory tract. <bold>Objectives:</bold> Evaluate the diagnostic and prognostic utility of miRNAs in EBC for lung cancer patients in India. <bold>Method:</bold> EBC was collected from 30 healthy and 30 patients with confirmed LC using R-tube. miRNA was isolated followed by cDNA preparation and miRNAs array was performed. The differentially expressed miRNAs were identified. Subsequently, miRNAs were validated in the EBC collected from the same groups. Further, the identified miRNAs were checked in bronchial brushings taken from normal and abnormal lesions. All the LC Patients were followed up for 6 months and identified miRNAs was examined. Data were analyzed using R-programming. <bold>Results:</bold> 30 healthy (Age/SD: 46.2/15.4, Male/%: 22/73), 30 LC patients (Age/SD: 56.7/10.3, Male/%: 23/76) were enrolled. The levels of 78 miRNAs were significantly altered in EBC of LC patients compared with healthy. Of these, six miRNAs were shortlisted for validation. Three miRNAs (let7i, miR-449c, and miR-31–3p) were upregulated in LC compared with healthy subjects with high accuracy. Interestingly, the expression of the identified miRNAs in EBC was negatively correlated with the bronchial brushings. Further, these three miRNAs were found to be down regulated in responders but remained stable in non-responders. <bold>Conclusion:</bold> We concluded that the miRNAs signatures in EBC is associated with LC and could be useful for diagnostic and prognostic biomarker for LC.