Circulating Small Extracellular Vesicle RNA Profiling for the Detection of T1a stage Colorectal Cancer and Precancerous Advanced Adenoma

Author:

Min Li12,Bu Fanqin2,Meng Jingxin2,Liu Xiang3,Guo Qingdong1,Zhao Libo3,Li Zhi3,Li Xiangji4,Zhu Shengtao1,Zhang Shutian1

Affiliation:

1. Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease

2. Key Laboratory of Bio-inspired Materials and Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences

3. Echo Biotech Co., Ltd

4. Department of Retroperitoneal Tumor Surgery, International Hospital, Peking University

Abstract

It takes more than twenty years for normal colorectal mucosa to develop into metastatic carcinoma. The long time window provides a golden opportunity for early detection to terminate the malignant progression. Here we aim to enable liquid biopsy of T1a stage colorectal cancer (CRC) and precancerous advanced adenoma (AA) by profiling circulating small extracellular vesicle (sEV)-derived RNAs. We exhibited a full RNA landscape for the circulating sEVs isolated from 60 participants. A total of 58,333 annotated RNAs were detected from plasma sEVs, among which 1,615 and 888 sEV-RNAs were found differentially expressed in plasma from T1a stage CRC and AA compared to normal controls (NC). Then we further categorized these sEV-RNAs into 6 modules by a weighted gene coexpression network analysis and constructed a 60-gene t-SNE model consisting of the top 10 RNAs of each module that could well distinguish T1a stage CRC/AA from NC samples. Some sEV-RNAs were also identified as indicators of specific endoscopic and morphological features of different colorectal lesions. The top-ranked biomarkers were further verified by RT-qPCR, proving that these candidate sEV-RNAs successfully identified T1a stage CRC/AA from NC in another cohort of 124 participants. Finally, we adopted different algorithms to improve the performance of RT-qPCR-based models and successfully constructed an optimized classifier with 79.3% specificity and 99.0% sensitivity. In conclusion, circulating sEVs of T1a stage CRC and AA patients have distinct RNA profiles, which successfully enable the detection of both T1a stage CRC and AA via liquid biopsy.

Publisher

eLife Sciences Publications, Ltd

Reference46 articles.

1. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries;CA Cancer J Clin,2021

2. Cancer statistics in China, 2015;CA Cancer J. Clin,2016

3. Jemal A. Cancer Statistics, 2017;CA Cancer J. Clin,2017

4. Cytoplasmic Asporin promotes cell migration by regulating TGF- β/Smad2/3 pathway and indicates a poor prognosis in colorectal cancer;Cell Death Dis,2019

5. Long-term oncological outcomes of local excision versus radical resection for early colorectal cancer in young patients without preoperative chemoradiotherapy: a population-based propensity matching study;Cancer Med,2018

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3