Abstract
Lung cancer remains to be the leading cause of cancer-related mortality worldwide. Finding new noninvasive biomarkers for lung cancer is still a significant clinical challenge. Exosomes are membrane-bound, nano-sized vesicles that are released by various living cells. Studies on exosomal proteomics may provide clues for developing clinical assays. In this study, we performed semi-quantitative proteomic analysis of proteins that were purified from exosomes of NCI-H838 non-small cell lung cancer cell line, with total cellular membrane proteins as control. In the exosomes, LC-MS/MS by data-independent analysis mode identified 3235 proteins. THBS1, ANXA6, HIST1H4A, COL18A1, MDK, SRGN, ENO1, TUBA4A, SLC3A2, GPI, MIF, MUC1, TALDO1, SLC7A5, ICAM1, HSP90AA1, G6PD, and LRP1 were found to be expressed in exosomes at more than 5-fold higher level as compared to total cellular membrane proteins. A well-known cancer biomarker, MUC1, is expressed at 8.98-fold higher in exosomes than total cellular membrane proteins. Subsequent analysis of plasma exosomes from non-small cell lung cancer (NSCLC) patients by a commercial electrochemiluminescence immunoassay showed that exosomal MUC1 level is 1.5-fold higher than healthy individuals (mean value 1.55 ± 0.16 versus mean value 1.05 ± 0.06, p = 0.0213). In contrast, no significant difference of MUC1 level was found between NSCLC patients and healthy individuals′ plasma (mean value 5.48 ± 0.65 versus mean value 4.16 ± 0.49). These results suggest that certain proteins, such as MUC1, are selectively enriched in the exosome compartment. The mechanisms for their preferential localization and their biological roles remain to be studied.
Highlights
Lung cancer is one of the most fatal malignancies and the leading cause of tumor mortality in both men and women in the world, with the incidence of 1.8 million new cases and 1.6 million death per year [1,2]
Traditional diagnosis of non-small cell lung cancer (NSCLC) tends to be based on X-ray, computerized tomography (CT), and pneumonocentesis [10]
Vykoukal et al reported the proteomics analysis of plasma-derived exosomes in lung adenocarcinoma patients (13 cases versus 15 controls). They reported that SRGN, TPM3, THBS1, HUWE1, and CCDC18 were enriched in lung adenocarcinoma extracellular vesicles
Summary
Lung cancer is one of the most fatal malignancies and the leading cause of tumor mortality in both men and women in the world, with the incidence of 1.8 million new cases and 1.6 million death per year [1,2]. Surgery is the recommended treatment for patients with stage I–II diseases [4,5]. Five-year survival is 77–92%, 68%, 60%, and 53% for clinical stage IA, IB, IIA, and IIB, respectively [6,7]. In all NSCLC cases, approximately 75% cases were diagnosed at advanced stage of disease, and the five-year overall survival rate is only 15% for all stages’ patients in spite of recent development of targeted therapy and immune blockade antibodies [8,9]. It has been estimated that less than 30% of cases can be detected at an early stage when the curative surgery is possible [11]
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