Extracellular Vesicles-derived CXCL4 is a Candidate Serum Tumor Biomarker for Colorectal Cancer

Overview

Journal iScience

Publisher Cell Press

Date 2024 Apr 18

PMID 38632995

Authors

Jinye Xie

Shan Xing

Hongbo Jiang

Jiaju Zhang

Daxiao Li

Shiqiong Niu

Zhijian Huang

Haofan Yin

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs) were promising circulating biomarkers for multiple diseases, but whether serum EVs-derived proteins could be used as a reliable tumor biomarker for colorectal cancer (CRC) remained inconclusive. In this study, we identified CXCL4 by a 4D data-independent acquisition-based quantitative proteomics assay of serum EVs-derived proteins in 40 individuals and subsequently analyzed serum EVs-derived CXCL4 levels by ELISA in 2 cohorts of 749 individuals. The results revealed that EVs-derived CXCL4 levels were dramatically elevated in CRC patients than in benign colorectal polyp patients or healthy controls (HC). Furthermore, receiver operating characteristic curves revealed that EVs-derived CXCL4 exhibited superior diagnostic performance with area under the curve of 0.948 in the training cohort. Additionally, CXCL4 could effectively distinguish CRC in stage I/II from HC. Notably, CRC patients with high levels of EVs-derived CXCL4 have shorter 2-year progression-free survival than those with low levels. Overall, our findings demonstrated that serum EVs-derived CXCL4 was a candidate diagnostic and prognostic biomarker for CRC.

References

Affandi A, Carvalheiro T, Ottria A, de Haan J, Brans M, Brandt M . CXCL4 drives fibrosis by promoting several key cellular and molecular processes. Cell Rep. 2022; 38(1):110189. DOI: 10.1016/j.celrep.2021.110189. View

Liu X, Song J, Zhang H, Liu X, Zuo F, Zhao Y . Immune checkpoint HLA-E:CD94-NKG2A mediates evasion of circulating tumor cells from NK cell surveillance. Cancer Cell. 2023; 41(2):272-287.e9. DOI: 10.1016/j.ccell.2023.01.001. View

Biller L, Schrag D . Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA. 2021; 325(7):669-685. DOI: 10.1001/jama.2021.0106. View

Zhang L, Shay J . Multiple Roles of APC and its Therapeutic Implications in Colorectal Cancer. J Natl Cancer Inst. 2017; 109(8). PMC: 5963831. DOI: 10.1093/jnci/djw332. View

Lin H, Zhang W, Xu Y, You Z, Zheng M, Liu Z . 4D label-free quantitative proteomics analysis to screen potential drug targets of Jiangu Granules treatment for postmenopausal osteoporotic rats. Front Pharmacol. 2022; 13:1052922. PMC: 9663813. DOI: 10.3389/fphar.2022.1052922. View

Joseph R, Soundararajan R, Vasaikar S, Yang F, Allton K, Tian L . CD8 T cells inhibit metastasis and CXCL4 regulates its function. Br J Cancer. 2021; 125(2):176-189. PMC: 8292398. DOI: 10.1038/s41416-021-01338-5. View

Chen I, Xue L, Hsu C, Paez Paez J, Pan L, Andaluz H . Phosphoproteins in extracellular vesicles as candidate markers for breast cancer. Proc Natl Acad Sci U S A. 2017; 114(12):3175-3180. PMC: 5373352. DOI: 10.1073/pnas.1618088114. View

Keum N, Giovannucci E . Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019; 16(12):713-732. DOI: 10.1038/s41575-019-0189-8. View

Quemener C, Baud J, Boye K, Dubrac A, Billottet C, Soulet F . Dual Roles for CXCL4 Chemokines and CXCR3 in Angiogenesis and Invasion of Pancreatic Cancer. Cancer Res. 2016; 76(22):6507-6519. DOI: 10.1158/0008-5472.CAN-15-2864. View

10.

Engle D, Tiriac H, Rivera K, Pommier A, Whalen S, Oni T . The glycan CA19-9 promotes pancreatitis and pancreatic cancer in mice. Science. 2019; 364(6446):1156-1162. PMC: 6705393. DOI: 10.1126/science.aaw3145. View

11.

Lai J, Chau Z, Chen S, Hill J, Korpany K, Liang N . Exosome Processing and Characterization Approaches for Research and Technology Development. Adv Sci (Weinh). 2022; 9(15):e2103222. PMC: 9130923. DOI: 10.1002/advs.202103222. View

12.

Xu T, Zhao J, Wang X, Meng Y, Zhao Z, Bao R . CXCL4 promoted the production of CD4CD25FOXP3treg cells in mouse sepsis model through regulating STAT5/FOXP3 pathway. Autoimmunity. 2020; 53(5):289-296. DOI: 10.1080/08916934.2020.1777283. View

13.

Cai J, Sun L, Gonzalez F . Gut microbiota-derived bile acids in intestinal immunity, inflammation, and tumorigenesis. Cell Host Microbe. 2022; 30(3):289-300. PMC: 8923532. DOI: 10.1016/j.chom.2022.02.004. View

14.

Yin H, Huang Z, Niu S, Ming L, Jiang H, Gu L . 5-Methylcytosine (mC) modification in peripheral blood immune cells is a novel non-invasive biomarker for colorectal cancer diagnosis. Front Immunol. 2022; 13:967921. PMC: 9532581. DOI: 10.3389/fimmu.2022.967921. View

15.

Min L, Zhu S, Chen L, Liu X, Wei R, Zhao L . Evaluation of circulating small extracellular vesicles derived miRNAs as biomarkers of early colon cancer: a comparison with plasma total miRNAs. J Extracell Vesicles. 2019; 8(1):1643670. PMC: 6691764. DOI: 10.1080/20013078.2019.1643670. View

16.

Bon L, Affandi A, Broen J, Christmann R, Marijnissen R, Stawski L . Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis. N Engl J Med. 2013; 370(5):433-43. PMC: 4040466. DOI: 10.1056/NEJMoa1114576. View

17.

Xie J, Huang Z, Jiang P, Wu R, Jiang H, Luo C . Elevated N6-Methyladenosine RNA Levels in Peripheral Blood Immune Cells: A Novel Predictive Biomarker and Therapeutic Target for Colorectal Cancer. Front Immunol. 2021; 12:760747. PMC: 8515146. DOI: 10.3389/fimmu.2021.760747. View

18.

Ren J, Lu P, Zhou X, Liao Y, Liu X, Li J . Genome-Scale Methylation Analysis of Circulating Cell-Free DNA in Gastric Cancer Patients. Clin Chem. 2021; 68(2):354-364. DOI: 10.1093/clinchem/hvab204. View

19.

Yu L, Yang X, Xu C, Sun J, Fang Z, Pan H . Comprehensive analysis of the expression and prognostic value of CXC chemokines in colorectal cancer. Int Immunopharmacol. 2020; 89(Pt B):107077. DOI: 10.1016/j.intimp.2020.107077. View

20.

Li C, Zhang D, Pang X, Pu H, Lei M, Fan B . Trajectories of Perioperative Serum Tumor Markers and Colorectal Cancer Outcomes: A Retrospective, Multicenter Longitudinal Cohort Study. EBioMedicine. 2021; 74:103706. PMC: 8605392. DOI: 10.1016/j.ebiom.2021.103706. View