Plasma Extracellular Vesicle Long RNAs Have Potential as Biomarkers in Early Detection of Colorectal Cancer

• Type of Material: Article
• Authors: Tian-An Guo, Fudan University; Hong-Yan Lai, Fudan University; Cong Li, Fudan University; Yan Li, Fudan University; Yu-Chen Li, Fudan University; Yu-Tong Jin, Fudan University; Zhao-Zhen Zhang, Emory University; Hao-Bo Huang, Fujian Medical University Union Hospital; Sheng-Lin Huang, Fudan University; Ye Xu, Fudan University
• Language: English
• Date: 2022-04-08
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Guo, Lai, Li, Li, Li, Jin, Zhang, Huang, Huang and Xu
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fonc.2022.829230
• Title of Journal or Parent Work: FRONTIERS IN ONCOLOGY
• Volume: 12
• Start Page: 829230
• End Page: 829230
• Grant/Funding Information: This work was supported by the National Natural Science Foundation of China (82072694, 81872294), the Shanghai Science and Technology Innovation Action Plan (20JC1419000), and the Shanghai Committee of Science and Technology (20DZ1100101, 19511121202).
• Keywords: long RNAs; colorectal cancer; Oncology; COLONOSCOPY; PROGNOSTIC BIOMARKER; SURVIVAL; extracellular vesicle; Life Sciences & Biomedicine; EXPRESSION; GENE; MICROARRAY; FEATURE-SELECTION; Science & Technology; colorectal adenoma; EXOSOMES; early detection

Abstract

Background: Early detection of colorectal cancer (CRC) is crucial to the treatment and prognosis of patients. Traditional screening methods have disadvantages. Methods: 231 blood samples were collected from 86 CRC, 56 colorectal adenoma (CRA), and 89 healthy individuals, from which extracellular vesicle long RNAs (exLRs) were isolated and sequenced. An CRC diagnostic signature (d-signature) was established, and prognosis-associated cell components were evaluated. Results: The exLR d-signature for CRC was established based on 17 of the differentially expressed exLRs. The d-signature showed high diagnostic efficiency of CRC and control (CRA and healthy) samples with an area under the curve (AUC) of 0.938 in the training cohort, 0.943 in the validation cohort, and 0.947 in an independent cohort. The d-signature could effectively differentiate early-stage (stage I–II) CRC from healthy individuals (AUC 0.990), as well as differentiating CEA-negative CRC from healthy individuals (AUC 0.988). A CRA d-signature was also generated and could differentiate CRA from healthy individuals both in the training (AUC 0.993) and validation (AUC 0.978) cohorts. The enrichment of class-switched memory B-cells, B-cells, naive B-cells, and mast cells showed increasing trends between CRC, CRA, and healthy cohorts. Class-switched memory B-cells, mast cells, and basophils were positively associated with CRC prognosis while natural killer T-cells, naive B-cells, immature dendritic cells, and lymphatic endothelial cells were negatively associated with prognosis. Conclusions: Our study identified that the exLR d-signature could differentiate CRC from CRA and healthy individuals with high efficiency and exLR profiling also has potential in CRA screening and CRC prognosis prediction.