Extracellular vesicles-derived CXCL4 is a candidate serum tumor biomarker for colorectal cancer

Jinye Xie; Shan Xing; Hongbo Jiang; Jiaju Zhang; Daxiao Li; Shiqiong Niu; Zhijian Huang; Haofan Yin

doi:10.1016/j.isci.2024.109612

Extracellular vesicles-derived CXCL4 is a candidate serum tumor biomarker for colorectal cancer

iScience. 2024 Mar 27;27(4):109612. doi: 10.1016/j.isci.2024.109612. eCollection 2024 Apr 19.

Authors

Jinye Xie¹, Shan Xing^{2

3}, Hongbo Jiang⁴, Jiaju Zhang⁵, Daxiao Li⁶, Shiqiong Niu⁴, Zhijian Huang⁷, Haofan Yin^{8

4}

Affiliations

¹ Department of Laboratory Medicine, Zhongshan City People's Hospital, Zhongshan, Guangdong, China.
² Department of Clinical Laboratory, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
³ School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, China.
⁴ Department of Clinical Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong, China.
⁵ Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
⁶ Department of Ophtalmology and ENT, Shenzhen Longgang District Second People's Hospital, Shenzhen, Guangdong, China.
⁷ Department of Pathology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China.
⁸ Department of Laboratory Medicine, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.

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.

Keywords: Cancer; medical science.