Abstract
Simple SummaryLung cancer, including non-small cell lung cancer, is the leading cause of cancer-related death worldwide. A better prognosis is associated with early diagnosis of lung cancer patients. Although annual screening guidelines for lung cancer are recommended, using various tools such as chest X-ray, low-dose computed tomography, and positron emission tomography, these screening procedures are expensive and difficult to repeat. They are also invasive and have a high risk of radiation exposure. Therefore, a low-risk, convenient diagnostic method using liquid biopsy and biomarkers is required for the early diagnosis of lung cancer. The newly proposed biomarker GCC2 was identified through proteomic analysis of exosomes secreted from lung cancer cell lines. GCC2 expression levels in peripheral blood of the patients showed high specificity and sensitivity in early lung cancer, demonstrating that our novel exosomal biomarker GCC2 can greatly contribute to improving the diagnosis of lung cancer patients, even though it has been tested in only a few pilot studies.No specific markers have been identified to detect non-small cell lung cancer (NSCLC) cell-derived exosomes circulating in the blood. Here, we report a new biomarker that distinguishes between cancer and non-cancer cell-derived exosomes. Exosomes isolated from patient plasmas at various pathological stages of NSCLC, NSCLC cell lines, and human pulmonary alveolar epithelial cells isolated using size exclusion chromatography were characterized. The GRIP and coiled-coil domain-containing 2 (GCC2) protein, involved in endosome-to-Golgi transport, was identified by proteomics analysis of NSCLC cell line-derived exosomes. GCC2 protein levels in the exosomes derived from early-stage NSCLC patients were higher than those from healthy controls. Receiver operating characteristic curve analysis revealed the diagnostic sensitivity and specificity of exosomal GCC2 to be 90% and 75%, respectively. A high area under the curve, 0.844, confirmed that GCC2 levels could effectively distinguish between the exosomes. These results demonstrate GCC2 as a promising early diagnostic biomarker for NSCLC.
Highlights
Lung cancer is a leading cause of cancer-related death in the world, with non-small cell lung cancer (NSCLC) accounting for almost 85% of all lung cancers [1,2]
We report on the use of GRIP and coiled-coil domain-containing 2 (GCC2) as a specific biomarker to distinguish between cancer-specific exosomes and normal cell-derived exosomes isolated from the body fluids of NSCLC patients, which can improve the diagnosis of cancer
The exosomes derived from Human pulmonary alveolar epithelial cells (HPAEpiC) and healthy control plasmas were positive against the anti-CD63 antibody with gold nanoparticle tagged secondary antibody, as revealed by Transmission Electron Microscopy (TEM) analysis (Figure 1g)
Summary
Lung cancer is a leading cause of cancer-related death in the world, with non-small cell lung cancer (NSCLC) accounting for almost 85% of all lung cancers [1,2]. Adenocarcinoma is the most common type of lung cancer, accounting for approximately 40% of all lung cancers (squamous cell carcinoma 25–30% and large cell carcinoma 5–10% of all lung cancers) [3]. Clinical guidelines recommend annual screening for lung cancer through multiple methods such as chest X-rays, low-dose computed tomography (LDCT) scan, positron emission tomography (PET-CT), magnetic resonance imaging (MRI), and bronchoscopic or CT-guided needle biopsies [8]. These examination procedures are expensive, difficult to repeat, invasive, and have a high risk of radiation exposure [9]. Low-risk and convenient diagnostic methods are required for early lung cancer diagnosis
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