Hidden in plain sight – Extracellular vesicles in saliva and sputum as biomarkers of lung cancer

Abstract

Lung cancer causes the most deaths of any cancer worldwide. An important reason for this is the fact that the disease is often diagnosed too late. Easier methods for the early detection of lung cancer would therefore greatly contribute to the overall survival chance. Saliva and sputum are easily collectible bodily fluids that contain many biological molecules. Among these molecules may be profiles that are unique to lung cancer. Extracellular vesicles (EVs) are cell-derived vesicles secreted to transport cargo between cells. These vesicles are released by all known cell types and come in many shapes and sizes, with the subcategories of EVs mainly being separated by size and the biological route through which the vesicles were generated. EVs are found in all bodily fluids, including the saliva and sputum, and are thought to be a reflection of the state and the origin in which the cell that released them is currently in. EVs are known to carry a wide range of cargoes, namely a mix of selected lipids, proteins and even genetic information. As EVs arrive to other cells they are taken up, thereby inducing phenotypic changes in the recipient cells. Since multiple studies have described specific functions of EVs in the context of lung cancer and that certain molecules may be enriched specifically on those EVs that are derived from lung cancer cells, EVs may carry potentially useful biomarkers. Considering that EVs are retrieved from all bodily fluids, and that lung-derived vesicles are more abundant in sputum and saliva, there may be valuable information in these vesicles that can aid in the diagnosis of lung cancer. In this review, we investigate what sets lung cancer-derived EVs apart from healthy EVs and how these differences may be exploited in the future in a clinical setting. To this extent we collected and set out the most recently available literature on salivary or sputum-derived lung cancer EVs together with more established findings on the role of EVs in lung cancer and currently known lung-cancer biomarkers, and we discuss the future clinical implications of the information at hand.