Abstract
Cancer screening and diagnosis can be achieved by analyzing specific molecules within serum-derived extracellular vesicles (EVs). This study sought to profile EV-derived proteins to identify potential lung cancer biomarkers. EVs were isolated from 80 serum samples from healthy individuals and cancer patients via polyethylene glycol (PEG)-based precipitation and immunoaffinity separation using antibodies against CD9, CD63, CD81, and EpCAM. Proteomic analysis was performed using 2-D gel electrophoresis and matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI–TOF MS). The expression of proteins that were differentially upregulated in the EVs or tissue of lung cancer samples was validated by Western blotting. The area under the curve (AUC) was calculated to assess the predictability of each differentially expressed protein (DEP) for lung cancer. A total of 55 upregulated protein spots were selected, seven of which (CD5L, CLEC3B, ITIH4, SERFINF1, SAA4, SERFINC1, and C20ORF3) were found to be expressed at high levels in patient-derived EVs by Western blotting. Meanwhile, only the expression of EV CD5L correlated with that in cancer tissues. CD5L also demonstrated the highest AUC value (0.943) and was found to be the core regulator in a pathway related to cell dysfunction. Cumulatively, these results show that EV-derived CD5L may represent a potential biomarker—detected via a liquid biopsy—for the noninvasive diagnosis of lung cancer.
Highlights
Lung cancer is the leading cause of cancer-related deaths worldwide, with a fiveyear survival rate below 21% [1]
We investigated the relationship between the expression of candidate markers in extracellular vesicles (EVs) and cancer tissues, and proposed an EV biomarker—detectable via a liquid biopsy—that may prove useful for lung cancer screening and diagnosis
The results suggest that CD5L can be used as a lung cancer-specific EV biomarker for liquid biopsy because its expression is linked to cancer origin, and it represents a core regulatory molecule with respect to functions associated with lung cancer
Summary
Lung cancer is the leading cause of cancer-related deaths worldwide, with a fiveyear survival rate below 21% [1]. It is categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), which constitute 15% and 85% of the lung cancer cases, respectively [2]. Liquid biopsy has been developed as an added tool for screening and early detection of cancer [6]. This technique has the potential to improve the survival rates of patients with various cancers, including lung cancer. Detection and surgical dissection of NSCLC, such as adenocarcinoma (AC) and squamous cell carcinoma (SCC), at stage I are associated with favorable five-year survival rates of 70–90% [7]
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