Abstract
Simple SummaryExosomes are an emerging source of cancer biomarkers. Molecular components of serum-derived exosomes have been addressed in several reports in the context of biomarkers for early detection of lung cancer. However, despite the promising results of pilot studies, the clinical applicability of such biomarkers has not been validated yet. In this review, the diagnostic potential of miRNA content of serum-derived exosomes is presented. Moreover, potential target genes and signaling pathways affected by miRNA present in lung cancer signatures are discussed.Early detection of lung cancer in screening programs is a rational way to reduce mortality associated with this malignancy. Low-dose computed tomography, a diagnostic tool used in lung cancer screening, generates a relatively large number of false-positive results, and its complementation with molecular biomarkers would greatly improve the effectiveness of such programs. Several biomarkers of lung cancer based on different components of blood, including miRNA signatures, were proposed. However, only a few of them have been positively validated in the context of early cancer detection yet, which imposes a constant need for new biomarker candidates. An emerging source of cancer biomarkers are exosomes and other types of extracellular vesicles circulating in body fluids. Hence, different molecular components of serum/plasma-derived exosomes were tested and showed different levels in lung cancer patients and healthy individuals. Several studies focused on the miRNA component of these vesicles. Proposed signatures of exosome miRNA had promising diagnostic value, though none of them have yet been clinically validated. These signatures involved a few dozen miRNA species overall, including a few species that recurred in different signatures. It is worth noting that all these miRNA species have cancer-related functions and have been associated with lung cancer progression. Moreover, a few of them, including known oncomirs miR-17, miR-19, miR-21, and miR-221, appeared in multiple miRNA signatures of lung cancer based on both the whole serum/plasma and serum/plasma-derived exosomes.
Highlights
Lung cancer is among the major cancer-related public health problem responsible for about a quarter of cancer-related deaths worldwide
MicroRNA component of serum/plasma is an attractive source of cancer biomarkers, and several miRNA signatures of lung cancer have been proposed
Though none of them is applied in clinical practice yet, a few are currently tested in prospective clinical trials aimed at validation of their applicability in the early detection of lung cancer and/or diagnosis of the indeterminate pulmonary nodules
Summary
Lung cancer is among the major cancer-related public health problem responsible for about a quarter of cancer-related deaths worldwide. There is an urgent need for clinical and molecular tests supporting CT-based screening for the detection of lung cancer to reduce “over-diagnosis” and decrease the costs. Potential biomarkers for early lung cancer can be found in various biological fluids; blood is the richest and most readily available source [10,11] Candidates for such biomarkers include serum proteins, free nucleic acids, and metabolites [11,12]. One of them is the autoantigen-based EarlyCDT-Lung test, which enables the classification of indeterminate nodules with a positive predictive value (PPV) >70% [23] Another test is the XL2 test, which combines the clinical probability of cancer score with the level of two plasma proteins: LG3BP and C163A [24]. The purpose of this literature review is to summarize current data on the emerging biomarker of early lung cancer-circulating serum exosomes and their microRNA cargo
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