CD5L as an Extracellular Vesicle-Derived Biomarker for Liquid Biopsy of Lung Cancer

被引:53
作者
Choi, Eun-Sook [1 ]
Al Faruque, Hasan [1 ]
Kim, Jung-Hee [2 ]
Kim, Kook Jin [3 ]
Choi, Jin Eun [4 ]
Kim, Bo A. [3 ]
Kim, Bora [3 ]
Kim, Ye Jin [3 ]
Woo, Min Hee [3 ]
Park, Jae Yong [5 ,6 ]
Hur, Keun [4 ]
Lee, Mi-Young [7 ]
Kim, Dong Su [3 ]
Lee, Shin Yup [5 ,6 ]
Kim, Eunjoo [2 ]
机构
[1] Daegu Gyeongbuk Inst Sci & Technol DGIST, Div Bifus Res, Techno Jungangdaero 333, Dague 42988, South Korea
[2] Daegu Gyeongbuk Inst Sci & Technol DGIST, Div Elect Informat Syst Res, Techno Jungangdaero 333, Dague 42988, South Korea
[3] Genomine Inc, Genomine Res Div, Pohang Technopk, Pohang 37668, South Korea
[4] Kyungpook Natl Univ, Sch Med, Dept Biochem, Daegu 41944, South Korea
[5] Kyungpook Natl Univ, Sch Med, Dept Internal Med, Daegu 41944, South Korea
[6] Kyungpook Natl Univ, Lung Canc Ctr, Chilgok Hosp, Daegu 41404, South Korea
[7] Soonchunhyang Univ, Dept Med Sci, Asan 31538, South Korea
关键词
lung cancer; extracellular vesicle; exosome; CD5L; 2-D gel electrophoresis; proteomics; biomarker; liquid biopsy;
D O I
10.3390/diagnostics11040620
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页数:18
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