Exosomal ncRNAs in liquid biopsy: a new paradigm for early cancer diagnosis and monitoring - Review

Sep 23, 2026

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Cancer’s aggressive biology and late diagnosis often lead to poor outcomes, making early detection and reliable monitoring essential. Traditional tumor biomarkers such as beta-2 microglobulin and CEA can produce inaccurate or inconclusive results. This review summarizes how exosomal cargoes, particularly non-coding RNAs including microRNAs, long non-coding RNAs, and circular RNAs, provide promising non-invasive biomarkers for early cancer diagnosis and follow-up, while also addressing current clinical limitations and key implementation challenges.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Introduction

Cancer burden and need for early diagnosis

Conventional diagnostic methods and limitations

Liquid biopsy as a non-invasive strategy

Exosomes and their biological roles

Exosomal ncRNAs and biomarker potential

Types of exosomal non-coding RNAs

Diagnostic performance examples

Challenges for clinical translation

TYPE Review PUBLISHED 09 July 2025 DOI 10.3389/fonc.2025.1615433 OPEN ACCESS EDITED BY Abdelbaset Mohamed Elasbali, Jouf University College of Applied Medical Science Qurayyat, Saudi Arabia REVIEWED BY Husam Qanash, University of Ha’ il, Saudi Arabia Hamad Alanazi, Al Jouf University, Saudi Arabia *CORRESPONDENCE Liqun Yang cysylq@swu [edu.cn](edu.cn) Xiaoxue Ke [kexiaoxue@126.com](kexiaoxue@126.com) †These authors contributed equally to this work RECEIVED 21 April 2025 ACCEPTED 06 June 2025 PUBLISHED 09 July 2025 CITATION Ghani MU, Du L, Moqbel AQ, Zhao E, Cui H, Yang L and Ke X (2025) Exosomal ncRNAs in liquid biopsy: a new paradigm for early cancer diagnosis and monitoring. Front. Oncol. 15:1615433 . doi: 10.3389/fonc.2025.1615433 COPYRIGHT © 2025 Ghani, Du, Moqbel, Zhao, Cui, Yang and Ke. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Exosomal ncRNAs in liquid biopsy: a new paradigm for early cancer diagnosis and monitoring Muhammad Usman Ghani 1†, Liang Du 2†, Abdulkareem Qasem Moqbel 1, Erhu Zhao 1, Hongjuan Cui 1, Liqun Yang 1* and Xiaoxue Ke 1* 1 Medical Research Institute, State Key Laboratory of Resource Insects, Southwest University, Chongqing, China, 2College of Biological Sciences and Biotechnology, Beijing Forestry University, Beijing, China Cancer ’s aggressive nature and delayed diagnoses often result in poor prognoses and limited treatment outcomes. Early detection, personalized treatments, and effective monitoring are essential for improving cancer management. Traditional tumor biomarkers, such as beta-2 microglobulin and Carcinoembryonic Antigen (CEA), are often yield inaccurate and inconclusive results. Recently, exosomal cargoes, especially non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have gained attention as promising tools for the early, non-invasive detection of cancer. For instance, serum exosomal long ncRNA FOXD2-AS1 has demonstrated promising diagnostic potential in colorectal cancer (CRC), achieving an overall AUC of 0.736 across all patients and an improved AUC of 0.758 speciﬁcally for early-stage CRC, highlighting its effectiveness as a stage-speciﬁc biomarker for early detection and clinical assessment. Similarly, exosoma l lncRNA-GC1 has effectively distinguished gastric cancer patients from controls and related conditions, with AUCs exceeding 0 . 86, thereby outperforming traditional markers such as CA 72- 4, CEA, and CA19-9, which all scored below 0 .79. Despite their great potential, the clinical application exosomal ncRNAs remains limited. This review highlights recent advancements in exosomal ncRNA research and their potential as diagnostic markers, addressing both the opportunities and challenges for clinical implementation. KEYWORDS exosomal ncRNA, miRNAs, lncRNAs, circRNAs, biomarkers, liquid biopsies, non-invasive Frontiers in Oncology 01 [frontiersin.org](frontiersin.org) Ghani et al. 10.3389/fonc.2025.1615433 GRAPHICAL ABSTRACT 1 Introduction Cancer is a multifaceted and formidable disease that presents asigniﬁcant risk to global health. It occurs when a cell’s genetic material is mutated, leading to abnormal cell division and unresponsiveness to the body’s natural defense system. Despite signiﬁcant research advancements over recent decades, it remains the second most commonly diagnosed disease and the ﬁfth leading cause of death among non-infectious diseases worldwide (1) . Prompt diagnosis is crucial, as it signiﬁcantly improves treatment, prog

FAQs

Why is early cancer diagnosis and monitoring important?

Early detection improves treatment decisions, prognosis, and overall survival. Timely monitoring helps assess disease status more effectively.

What limits traditional tumor biomarkers in clinical practice?

Conventional biomarkers like beta-2 microglobulin and CEA may yield inaccurate or inconclusive results, which reduces diagnostic reliability.

Which exosomal RNA types are highlighted as promising liquid biopsy markers?

The review emphasizes non-coding RNAs carried by exosomes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs).

What are the main challenges for clinical use of exosomal ncRNAs?

Despite strong potential, clinical application remains limited due to obstacles in real-world implementation, including practical and translational challenges for routine diagnosis.

Sep 23, 2026

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