Landscape of extracellular small RNA and identification of biomarkers in multiple human cancers

Summary: Extracellular RNAs (exRNAs) in biofluids, sourced from diverse tissues, exhibit various biological functions and diagnostic potential. Small non-coding RNAs, such as rsRNAs and tsRNAs, are abundant in tissues and likely secreted into biofluids, contributing to exRNA profiles. To comprehensi...

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Main Authors: Shoubin Zhan, Ye Xu, Botao Li, Peng Ge, Chunwu Zhang, Shengkai Zhou, Tingting Yang, Gaoli Liang, Ling Ji, Xiangbin Kong, Ping Yang, Xi Chen, Chen-Yu Zhang, Han Shen, Xu Luo, Zhen Zhou, Yanbo Wang
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Language:English
Published: Elsevier 2025-08-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225013598
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author Shoubin Zhan
Ye Xu
Botao Li
Peng Ge
Chunwu Zhang
Shengkai Zhou
Tingting Yang
Gaoli Liang
Ling Ji
Xiangbin Kong
Ping Yang
Xi Chen
Chen-Yu Zhang
Han Shen
Xu Luo
Zhen Zhou
Yanbo Wang
author_facet Shoubin Zhan
Ye Xu
Botao Li
Peng Ge
Chunwu Zhang
Shengkai Zhou
Tingting Yang
Gaoli Liang
Ling Ji
Xiangbin Kong
Ping Yang
Xi Chen
Chen-Yu Zhang
Han Shen
Xu Luo
Zhen Zhou
Yanbo Wang
author_sort Shoubin Zhan
collection DOAJ
description Summary: Extracellular RNAs (exRNAs) in biofluids, sourced from diverse tissues, exhibit various biological functions and diagnostic potential. Small non-coding RNAs, such as rsRNAs and tsRNAs, are abundant in tissues and likely secreted into biofluids, contributing to exRNA profiles. To comprehensively evaluate exRNAs, we employed traditional and enzymatic treatment RNA sequencing to systematically profile exRNAs across six human biofluids including serum, ascites, urine, milk, seminal plasma and saliva as well as sera from mice, rats, rabbits, and bovines. rsRNAs were identified as the most abundant exRNA species in human biofluids, with rsRNAs and tsRNAs showing high expression and species-specific profiles across animals. In serum samples from 51 healthy individuals and 69 cancer patients, exRNA-based machine learning model achieved 94.1% sensitivity and 100% specificity in cancer detection and accurately classified tumor origin. Altogether, this study reveals distinct rsRNA-abundant exRNA landscape across multiple biofluids and support the potential of exRNA signatures in pan-cancer diagnostics.
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spelling doaj-art-8f0052ef2dc44907a1ff0dff85c943fc2025-08-20T03:44:27ZengElsevieriScience2589-00422025-08-0128811309810.1016/j.isci.2025.113098Landscape of extracellular small RNA and identification of biomarkers in multiple human cancersShoubin Zhan0Ye Xu1Botao Li2Peng Ge3Chunwu Zhang4Shengkai Zhou5Tingting Yang6Gaoli Liang7Ling Ji8Xiangbin Kong9Ping Yang10Xi Chen11Chen-Yu Zhang12Han Shen13Xu Luo14Zhen Zhou15Yanbo Wang16Department of Clinical Laboratory, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Nanjing University, Nanjing 210023, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Nanjing University, Nanjing 210023, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Nanjing University, Nanjing 210023, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Nanjing University, Nanjing 210023, ChinaNational Key Clinical Specialty (Wound Healing), Department of Wounds and Burns, Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Nanjing University, Nanjing 210023, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Nanjing University, Nanjing 210023, China; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Nanjing University, Nanjing 210023, ChinaNational Key Clinical Specialty (Wound Healing), Department of Wounds and Burns, Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaNational Key Clinical Specialty (Wound Healing), Department of Wounds and Burns, Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, ChinaDepartment of Clinical Laboratory, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Nanjing University, Nanjing 210023, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Nanjing University, Nanjing 210023, ChinaDepartment of Clinical Laboratory, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; Corresponding authorNational Key Clinical Specialty (Wound Healing), Department of Wounds and Burns, Key Laboratory of Intelligent Treatment and Life Support for Critical Diseases of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Corresponding authorState Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Nanjing University, Nanjing 210023, China; Corresponding authorDepartment of Clinical Laboratory, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China; State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), Nanjing University, Nanjing 210023, China; Corresponding authorSummary: Extracellular RNAs (exRNAs) in biofluids, sourced from diverse tissues, exhibit various biological functions and diagnostic potential. Small non-coding RNAs, such as rsRNAs and tsRNAs, are abundant in tissues and likely secreted into biofluids, contributing to exRNA profiles. To comprehensively evaluate exRNAs, we employed traditional and enzymatic treatment RNA sequencing to systematically profile exRNAs across six human biofluids including serum, ascites, urine, milk, seminal plasma and saliva as well as sera from mice, rats, rabbits, and bovines. rsRNAs were identified as the most abundant exRNA species in human biofluids, with rsRNAs and tsRNAs showing high expression and species-specific profiles across animals. In serum samples from 51 healthy individuals and 69 cancer patients, exRNA-based machine learning model achieved 94.1% sensitivity and 100% specificity in cancer detection and accurately classified tumor origin. Altogether, this study reveals distinct rsRNA-abundant exRNA landscape across multiple biofluids and support the potential of exRNA signatures in pan-cancer diagnostics.http://www.sciencedirect.com/science/article/pii/S2589004225013598OncologyDiagnosticsTranscriptomics
spellingShingle Shoubin Zhan
Ye Xu
Botao Li
Peng Ge
Chunwu Zhang
Shengkai Zhou
Tingting Yang
Gaoli Liang
Ling Ji
Xiangbin Kong
Ping Yang
Xi Chen
Chen-Yu Zhang
Han Shen
Xu Luo
Zhen Zhou
Yanbo Wang
Landscape of extracellular small RNA and identification of biomarkers in multiple human cancers
iScience
Oncology
Diagnostics
Transcriptomics
title Landscape of extracellular small RNA and identification of biomarkers in multiple human cancers
title_full Landscape of extracellular small RNA and identification of biomarkers in multiple human cancers
title_fullStr Landscape of extracellular small RNA and identification of biomarkers in multiple human cancers
title_full_unstemmed Landscape of extracellular small RNA and identification of biomarkers in multiple human cancers
title_short Landscape of extracellular small RNA and identification of biomarkers in multiple human cancers
title_sort landscape of extracellular small rna and identification of biomarkers in multiple human cancers
topic Oncology
Diagnostics
Transcriptomics
url http://www.sciencedirect.com/science/article/pii/S2589004225013598
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