Tim4-Functionalized (EV)-E-HB-Chip by Isolating Plasma-Derived Phosphatidylserine-Positive Small Extracellular Vesicles for Pan-Cancer Screening

作者全名："Yang, Liu; Tong, Xuedong; Zhang, Yong; Li, Yan; Liu, Jiangwei; Yin, Ruiling; Zeng, Dong; Yuan, Yue; Deng, Kun"

作者地址："[Yang, Liu; Tong, Xuedong; Zhang, Yong; Li, Yan; Liu, Jiangwei; Yin, Ruiling; Zeng, Dong; Yuan, Yue; Deng, Kun] Chongqing Med Univ, Affiliated Hosp 3, Dept Lab Med, 1 Shuanghu Branch Rd, Chongqing 400016, Peoples R China"

通信作者："Deng, K (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Lab Med, 1 Shuanghu Branch Rd, Chongqing 400016, Peoples R China."

来源：ADVANCED MATERIALS TECHNOLOGIES

ESI学科分类：MATERIALS SCIENCE

WOS号：WOS:000736702800001

JCR分区：Q1

影响因子：6.8

年份：2022

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：microfluidic; pan-cancer screening; phosphatidylserine; small extracellular vesicles; Tim4

摘要："Thanks to containing tumor-related molecules, small extracellular vesicles (sEVs) are emerging as biomarkers in tumor liquid biopsy and commonly employed to diagnose a specific cancer. However, a pan-cancer screening method for pre-symptomatic patients is crucial to achieving the early cancer detection. Herein, a lipid-protein capture system on herringbone (HB) microfluidic chip ((EV)-E-HB-Chips) to isolate multiple tumor-derived sEVs is constructed. Phosphatidylserine (PS) is abnormally surface-supposed on tumor-derived sEVs and binds T-cell immunoglobulin domain and mucin domain-containing protein 4 (Tim4) in calcium-dependent manner. PS+ sEVs isolated by the (EV)-E-HB-Chips is perform on liquid chromatography electrospray ionization tandem mass spectrometry and it is found that PS+ sEVs are highly correlated with tumor-related pathway (P < 0.05), such as Cdc42 protein signal transduction, neuropilin signaling pathway, and Wnt signaling pathway. And it is further validated in clinical sample and found that PS(+)sEV number shows statistical difference between cancer patients and healthy donors in plasma (P < 0.01) and has efficient diagnostic power (area under curve = 0.86), suggesting PS(+)sEV as potential biomarker for pan-cancer screening. The Tim-4 functionalized device facilitates the early multiple cancer detection, providing the potential to be used as a rapid-screening tool in clinical setting."

基金机构："Chongqing Medical University COVID-19 Emergency Research Project [CQMUNP0211]; Chongqing postgraduate research innovation project [CYS19194]; Key project of the Third Affiliated Hospital of Chongqing Medical University [KY08028, KY19027]"

基金资助正文："This work was supported by Chongqing Medical University COVID-19 Emergency Research Project (CQMUNP0211), Chongqing postgraduate research innovation project (CYS19194), and Key project of the Third Affiliated Hospital of Chongqing Medical University (KY08028, KY19027)."