A Simple and Available Measurement of Onco-sEV DsDNA to Protein Ratio As a Potential Tumor Marker

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2023 Jul 3

PMID 37400751

Authors

Yifan Sun

Miao Li

Xiaoshan Zhang

Dongjie Xu

Jie Wu

Xinrui Gu

Adeel Khan

Han Shen

Zhiyang Li

Affiliations

Soon will be listed here.

Abstract

Background: Small extracellular vesicles (sEVs) have great potential as new biomarkers in liquid biopsy. However, due to the limitations of sEVs extraction and component analysis procedures, further clinical applications of sEVs are hampered. Carcinoembryonic antigen (CEA) is a commonly used broad-spectrum tumor marker that is strongly expressed in a variety of malignancies.

Results: In this study, CEA sEVs were directly separated from serum using immunomagnetic beads, and the nucleic acid to protein ultraviolet absorption ratio (NPr) of CEA sEVs was determined. It was found that the NPr of CEA sEVs in tumor group was higher than that of healthy group. We further analyzed the sEV-derived nucleic acid components using fluorescent staining and found that the concentration ratio of double-stranded DNA to protein (dsDPr) in CEA sEVs was also significantly different between the two groups, with a sensitivity of 100% and a specificity of 41.67% for the diagnosis of pan-cancer. The AUC of dsDPr combined with NPr was 0.87 and the ACU of dsDPr combined with CA242 could reach 0.94, showing good diagnostic performance for pan-cancer.

Conclusions: This study demonstrates that the dsDPr of CEA sEVs can effectively distinguish sEVs derived from tumor patients and healthy individuals, which can be employed as a simple and cost-effective non-invasive screening technology to assist tumor diagnosis.

References

Lin S, Yu Z, Chen D, Wang Z, Miao J, Li Q . Progress in Microfluidics-Based Exosome Separation and Detection Technologies for Diagnostic Applications. Small. 2019; 16(9):e1903916. DOI: 10.1002/smll.201903916. View

Li X, Hayward C, Fong P, Dominguez M, Hunsucker S, Lee L . A blood-based proteomic classifier for the molecular characterization of pulmonary nodules. Sci Transl Med. 2013; 5(207):207ra142. PMC: 4114963. DOI: 10.1126/scitranslmed.3007013. View

Diamond J, Vanpouille-Box C, Spada S, Rudqvist N, Chapman J, Ueberheide B . Exosomes Shuttle TREX1-Sensitive IFN-Stimulatory dsDNA from Irradiated Cancer Cells to DCs. Cancer Immunol Res. 2018; 6(8):910-920. PMC: 6072562. DOI: 10.1158/2326-6066.CIR-17-0581. View

Li K, Lin Y, Luo Y, Xiong X, Wang L, Durante K . A signature of saliva-derived exosomal small RNAs as predicting biomarker for esophageal carcinoma: a multicenter prospective study. Mol Cancer. 2022; 21(1):21. PMC: 8764835. DOI: 10.1186/s12943-022-01499-8. View

Guo X, Peng Y, Song Q, Wei J, Wang X, Ru Y . A Liquid Biopsy Signature for the Early Detection of Gastric Cancer in Patients. Gastroenterology. 2023; 165(2):402-413.e13. DOI: 10.1053/j.gastro.2023.02.044. View

Lee Y, Kim G, Tak W, Jang S, Kweon Y, Park J . Circulating exosomal noncoding RNAs as prognostic biomarkers in human hepatocellular carcinoma. Int J Cancer. 2018; 144(6):1444-1452. DOI: 10.1002/ijc.31931. View

Becker A, Thakur B, Weiss J, Kim H, Peinado H, Lyden D . Extracellular Vesicles in Cancer: Cell-to-Cell Mediators of Metastasis. Cancer Cell. 2016; 30(6):836-848. PMC: 5157696. DOI: 10.1016/j.ccell.2016.10.009. View

Li M, Tan J, Zhang Y, Ai C, Wang H, Zhang H . Assessing CT imaging features combined with CEA and CA125 levels to identify endometriosis-associated ovarian cancer. Abdom Radiol (NY). 2020; 46(6):2367-2375. DOI: 10.1007/s00261-020-02571-x. View

Jakobsen K, Paulsen B, Baek R, Varming K, Sorensen B, Jorgensen M . Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma. J Extracell Vesicles. 2015; 4:26659. PMC: 4348413. DOI: 10.3402/jev.v4.26659. View

10.

Sun D, Zhao Z, Spiegel S, Liu Y, Fan J, Amrollahi P . Dye-free spectrophotometric measurement of nucleic acid-to-protein ratio for cell-selective extracellular vesicle discrimination. Biosens Bioelectron. 2021; 179:113058. PMC: 7995647. DOI: 10.1016/j.bios.2021.113058. View

11.

Li Y, Zhang Y, Qiu F, Qiu Z . Proteomic identification of exosomal LRG1: a potential urinary biomarker for detecting NSCLC. Electrophoresis. 2011; 32(15):1976-83. DOI: 10.1002/elps.201000598. View

12.

Kishi J, Schaus T, Gopalkrishnan N, Xuan F, Yin P . Programmable autonomous synthesis of single-stranded DNA. Nat Chem. 2018; 10(2):155-164. PMC: 5784857. DOI: 10.1038/nchem.2872. View

13.

Nakano T, Chen I, Wang C, Chen P, Tseng H, Huang K . Circulating exosomal miR-92b: Its role for cancer immunoediting and clinical value for prediction of posttransplant hepatocellular carcinoma recurrence. Am J Transplant. 2019; 19(12):3250-3262. DOI: 10.1111/ajt.15490. View

14.

Vasconcelos M, Caires H, Abols A, Xavier C, Line A . Extracellular vesicles as a novel source of biomarkers in liquid biopsies for monitoring cancer progression and drug resistance. Drug Resist Updat. 2019; 47:100647. DOI: 10.1016/j.drup.2019.100647. View

15.

Lee S, Park H, Hur J, Kim H, Kim I, Kim W . Genomic profiling of extracellular vesicle-derived DNA from bronchoalveolar lavage fluid of patients with lung adenocarcinoma. Transl Lung Cancer Res. 2021; 10(1):104-116. PMC: 7867756. DOI: 10.21037/tlcr-20-888. View

16.

Zhang M, Hu S, Liu L, Dang P, Liu Y, Sun Z . Engineered exosomes from different sources for cancer-targeted therapy. Signal Transduct Target Ther. 2023; 8(1):124. PMC: 10017761. DOI: 10.1038/s41392-023-01382-y. View

17.

Liu H, Tian Y, Xue C, Niu Q, Chen C, Yan X . Analysis of extracellular vesicle DNA at the single-vesicle level by nano-flow cytometry. J Extracell Vesicles. 2022; 11(4):e12206. PMC: 8977970. DOI: 10.1002/jev2.12206. View

18.

Yaghoubi N, Avval F, Khazaei M, Sahebkar A, Aghaee-Bakhtiari S . High Diagnostic and Prognostic Value of miRNAs Compared with the Carcinoembryonic Antigen As A Traditional Tumor Marker. Anticancer Agents Med Chem. 2021; 22(2):206-214. DOI: 10.2174/1871520621666210608094908. View

19.

Chen Z, Liu L, Zhu F, Cai X, Zhao Y, Liang P . Dynamic monitoring serum tumor markers to predict molecular features of EGFR-mutated lung cancer during targeted therapy. Cancer Med. 2022; 11(16):3115-3125. PMC: 9385589. DOI: 10.1002/cam4.4676. View

20.

Spada S . Methods to purify DNA from extracellular vesicles: Focus on exosomes. Methods Enzymol. 2021; 645:109-118. DOI: 10.1016/bs.mie.2020.09.004. View