Serum Exosomes and Their miRNA Load—A Potential Biomarker of Lung Cancer

Abstract

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.

The Lipid Composition of Serum-Derived Small Extracellular Vesicles in Participants of a Lung Cancer Screening Study

“…Extracellular vesicles circulating in the biofluids of cancer patients, which represent a mixture of TEX and other classes of vesicles released by “normal” types of cells, are a potential source of diagnostic and prognostic biomarkers. Numerous studies tested protein and RNA components of such vesicles in the context of lung cancer [ 21 ]. Several lung cancer signatures were proposed based on proteins present in serum/plasma-derived sEV [ 22 , 23 , 24 , 31 , 32 ], and more reports focused on the miRNA cargo of serum/plasma-derived sEV.…”

“…Several lung cancer signatures were proposed based on proteins present in serum/plasma-derived sEV [ 22 , 23 , 24 , 31 , 32 ], and more reports focused on the miRNA cargo of serum/plasma-derived sEV. According to the current literature review, miRNA signatures of lung cancer have been reported in about 30 papers [ 21 ]. These signatures contained about 60 miRNA species overall, including 14 miRNA species that appeared in multiple signatures (exemplified by the oncomir miR-21).…”

“…However, there is only one study where the metabolite profile of sEV purified by ultracentrifugation from the plasma of lung cancer patients (44 cases and 39 controls) was reported [ 39 ]. The diagnostic potential of lung cancer signatures based on different molecular components of serum/plasma-derived sEV was tested in part of the abovementioned studies, which resulted in AUC values that ranged between 0.70 and 0.95 [ 21 ]. However, different protocols were used in these studies for sEV purification and characterization.…”

“…Hence, the overall serum/plasma sEV load remains a practical and potentially useful source of cancer biomarkers [ 20 ]. The diagnostic potential of serum sEV in lung cancer has been tested in several papers, mostly focused on their miRNA [ 21 ] and protein [ 22 , 23 , 24 ] cargo. However, none of the reported studies were based on material collected prospectively in the frame of a screening study; hence, the relevance of the resulting sEV-based molecular signatures for the early detection of lung cancer remains unclear.…”

miR-145-5p Mimic Inhibits Bone Metastasis of Prostate Cancer Via the Regulation of Epithelial Mesenchymal Transition

“…In this study, we found that the top 11 signi cantly changed miRNAs (hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-133a-3p, hsa-miR-222-5p, hsa-miR-204-3p, hsa-miR-145-5p, hsa-miR-3681-5p, hsa-miR-184, hsa-miR-144-3p, hsa-miR-204-5p, and hsa-miR-221-5p) were deregulated in prostate cancer with bone metastasis malignant transformation. It has been reported that miR-221 may be a potential prognostic biomarker of hepatocellular carcinoma, lung cancer, and breast cancer and a critical regulator of therapeutic susceptibility in breast cancer [21][22][23]. The active cells in bone include osteoblasts, osteoclasts, hematopoietic cells, adipocytes and various immune cells.…”