Abstract
Simple SummaryThe role of exosomes in HIV (human immunodeficiency virus) as well as in cancer patients seems to be pivotal. The aim of our retrospective study was to assess the potential clinical value of CD9-positive plasma exosomes in lung cancer patients, patients with lung granulomas, healthy individuals, and HIV-positive patients with or without lung cancer. This study shows that CD9-positive plasma exosome concentrations differ between healthy controls, patients with immunocompetent pulmonary granulomas and patients with lung cancer. In addition, CD9-positive plasma exosomes are increased in HIV seropositive and HIV seronegative lung cancer patients compared to healthy controls, while chemotherapy-treated lung cancer patients have lower plasma exosome levels. This study also shows that in chemotherapy-naïve patients, plasma exosome levels are directly correlated with a prognosis with higher concentrations being associated with a longer, overall survival. These findings further support previous literature on the translational significance of total plasma exosomes in cancer patients, despite different immunological contexts.Recently, the role of exosomes in the progression of both cancer and HIV (human immunodeficiency virus) has been described. This study investigates the clinical significance of CD9-positive plasma exosomes in lung cancer patients, healthy individuals, and HIV-positive patients with or without lung cancer. Using a verified with transmission electron microscopy double-sandwich ELISA technique, plasma-derived exosomes were isolated and quantified from 210 lung cancer patients (including 44 metastatic patients with progressive disease after chemotherapy), 49 healthy controls, 20 patients with pulmonary granulomas, 19 HIV+ patients with lung cancer, 31 HIV+ patients without cancer, and 3 HIV+ patients with pulmonary granulomas. Plasma exosome concentrations differed between healthy controls, patients with immunocompetent pulmonary granulomas and patients with lung cancer even after chemotherapy (p < 0.001). Lung cancer patients after chemotherapy had lower exosome concentrations compared to patients with untreated lung cancer or granuloma (p < 0.001 for both). HIV+ patients without lung cancer had significantly higher exosome concentrations compared to HIV+ patients with lung cancer (p = 0.016). Although exosome concentrations differed between all different lung cancer histologies and healthy controls (p < 0.001 for all histologies), adjusted statistical significance was oµy retained for patients with granulomas and SCLC (Small-cell lung cancer, p < 0.001). HIV-induced immunodeficient patients with or without lung cancer had lower plasma exosomes compared to immunocompetent granuloma and lung cancer patients (p < 0.001). Finally, higher plasma exosomes were associated both on univariate (p = 0.044), and multivariate analysis (p = 0.040) with a better 3-year survival in stage II and III NSCLC (Non-small-cell lung carcinoma) patients. In conclusion, our study shows that CD9-positive plasma exosomes are associated with both lung cancer and HIV, prior chemotherapy, as well as with survival, suggesting a possible prognostic value.
Highlights
Lung cancer remains the leading cause of cancer-related deaths worldwide
Plasma exosome concentrations were evaluated in 20 lung granuloma patients, who presented during the same time period for suspected cancer, but pathologically had a histologically confirmed benign disease
The data from this study convincingly show that plasma exosome concentration in patients is altered depending on medical history and that cancer, human immunodeficiency virus (HIV) immunopositivity, as well as systemically administered chemotherapy can influence the levels of CD9-posistive plasma exosomes
Summary
Lung cancer remains the leading cause of cancer-related deaths worldwide. Genetic and epigenetic knowledge of lung cancer pathobiology has impressively expanded over the years, only recently has there been substantial progress clinically with the implementation of immunotherapeutic agents and specific kinase inhibitors [1,2]. In the last five years especially, there has been a growing number of publications shedding light on the role of exosomes and their cargo in cancer pathogenesis [5]. Little is known about the role of primary-tumor-derived exosomes in lung cancer progression, their importance in determining organ-specific cancer metastasis by binding to corresponding matrix proteins in a distant organ has obvious clinical relevance [6,7]. Since metastases are responsible for most cancer deaths in solid tumors, understanding the functional differences between tumor-derived and non-tumor-derived exosomes is an area ripe for investigation
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