Xie Jinye, Xing Shan, Jiang Hongbo, Zhang Jiaju, Li Daxiao, Niu Shiqiong, Huang Zhijian, Yin Haofan
Department of Laboratory Medicine, Zhongshan City People's Hospital, Zhongshan, Guangdong, China.
Department of Clinical Laboratory, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China.
iScience. 2024 Mar 27;27(4):109612. doi: 10.1016/j.isci.2024.109612. eCollection 2024 Apr 19.
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.
细胞外囊泡（EVs）是多种疾病颇具前景的循环生物标志物，但血清EVs衍生蛋白能否作为结直肠癌（CRC）可靠的肿瘤生物标志物仍尚无定论。在本研究中，我们通过基于数据非依赖采集的定量蛋白质组学分析，在40名个体中鉴定出血清EVs衍生蛋白中的CXCL4，随后通过酶联免疫吸附测定（ELISA）在两组共749名个体中分析血清EVs衍生的CXCL4水平。结果显示，CRC患者血清EVs衍生的CXCL4水平显著高于良性结直肠息肉患者或健康对照（HC）。此外，受试者工作特征曲线显示，血清EVs衍生的CXCL4在训练队列中表现出卓越的诊断性能，曲线下面积为0.948。此外，CXCL4能够有效区分I/II期CRC患者与HC。值得注意的是，血清EVs衍生的CXCL4水平高的CRC患者无进展生存期2年短于水平低的患者。总体而言，我们的研究结果表明，血清EVs衍生的CXCL4是CRC的候选诊断和预后生物标志物。
