Abstract
This study represents a novel proof of concept of the clinical utility of miRNAs from exhaled breath condensate (EBC) as biomarkers of lung cancer (LC). Genome-wide miRNA profiling and machine learning analysis were performed on EBC from 21 healthy volunteers and 21 LC patients. The levels of 12 miRNAs were significantly altered in EBC from LC patients where a specific signature of miR-4507, miR-6777-5p and miR-451a distinguished these patients with high accuracy. Besides, a distinctive miRNA profile between LC adenocarcinoma and squamous cell carcinoma was observed, where a combined panel of miR-4529-3p, miR-8075 and miR-7704 enabling discrimination between them. EBC levels of miR-6777-5p, 6780a-5p and miR-877-5p predicted clinical outcome at 500 days. Two additional miRNA signatures were also associated with other clinical features such as stage and invasion status. Dysregulated EBC miRNAs showed potential target genes related to LC pathogenesis, including CDKN2B, PTEN, TP53, BCL2, KRAS and EGFR. We conclude that EBC miRNAs might allow the identification, stratification and monitorization of LC, which could lead to the development of precision medicine in this and other respiratory diseases.
Highlights
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide, with more than 1.8 million deaths in 2018, according to a GLOBOCAN2018 estimate [1]
We here show the proof of concept of the clinical utility of miRNAs from exhaled breath condensate (EBC) as non-invasive biomarkers for lung cancer
Three miRNAs including miR-1248, miR-1291 and let-7 were downregulated in asthma compared with COPD and healthy donors (HDs), while miR-328 and miR-21 were lower in both respiratory diseases compared with HDs [22]
Summary
Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide, with more than 1.8 million deaths in 2018, according to a GLOBOCAN2018 estimate [1]. The average 5-year survival rate of lung cancer is disappointingly low with a mortality rate of 85%. The two main types of NSLC are adenocarcinoma (AD) and squamous cell carcinoma (SCC, known as epidermoid carcinoma), which account for 30% and 25% of all lung cancers, respectively [2]. There have been recent advances in novel therapies for lung cancer, they are not effective at an advanced stage of the disease and, these treatments have not improved the prognosis for those patients [3]. An effective early screening test has been long sought to identify the disease in early stages, when treatments are much more effective. Chest radiography and sputum cytology have been tested in early screening trials, they were not effective in reducing lung cancer mortality rates [4]
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