Abstract
Lung cancer is the predominant cause of cancer-related deaths. The high mortality rates are mainly due to the lack of diagnosis before the cancer is at a late stage. Liquid biopsy is a promising technique that could allow early diagnosis of lung cancer and better treatment selection for patients. Cell-free microRNAs have been detected in biological fluids, such as serum and plasma, and are considered interesting biomarkers for lung cancer screening and detection. Exosomes are nanovesicles of 30–150 nm and can be released by different cell types within the tumor microenvironment. Their exosomal composition reflects that of their parental cells and could be potentially useful as a biomarker for lung cancer diagnosis. This review summarizes the state-of-the-art of circulating microRNAs (miRNAs) in lung cancer, focusing on their potential use in clinical practice. Moreover, we describe the importance of exosomal miRNA cargo in lung cancer detection and their potential role during lung carcinogenesis. Finally, we discuss our experience with the analysis of circulating exosomal miRNAs in the bioMILD screening trial.
Highlights
Lung cancer is a leading cause of cancer deaths globally for both men and women, accounting for more than 1.4 million deaths per year [1]
We focused on a cellular source of circulating miRNAs that are components of our miRNA Signature Classifier (MSC) risk classifier, and observed several miRNAs not being released by non-epithelial cells but, rather, by granulocytes and platelets, which represented a major contribution of miRNA release in blood [76]
The tumor microenvironment exerts a key role in lung carcinogenesis [13] and, in particular, extracellular vesicles show the ability to modulate the phenotype of the microenvironment cells that directly surround the primary tumor or the metastatic niche [85]
Summary
Lung cancer is a leading cause of cancer deaths globally for both men and women, accounting for more than 1.4 million deaths per year [1]. Lung cancer development and progression is strongly regulated by the complex interplay between a tumor and its microenvironment, which can include stromal cells such as fibroblast, endothelial, and immune cells [11,12] as well as biomolecules, such as several types of growth and inflammatory factors, and proteases [13]. Lung cancer progression is driven by a tumor’s underlying genetic alterations but is mediated by complex systemic interactions between cells in the tumor microenvironment by way of several mechanisms: cell–cell contacts (receptor-mediated interaction, gap junctions) or paracrine signals (growth factors, cytokines, and chemokines), as well as by extracellular vesicles (EVs), including exosomes [16]. We illustrate our data, obtained by investigating exosomes and their miRNA cargo in bioMILD screening trials, consolidating their important impact in detection, definition, diagnosis, and clinical management in lung malignancies
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