Circulating miRNAs as liquid biopsy biomarkers for diagnosis in patients with colorectal cancer: a systematic review and meta-analysis

ObjectiveColorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, emphasizing the need for noninvasive and reliable diagnostic tools. Circulating microRNAs (miRNAs) have emerged as promising liquid biopsy biomarkers for CRC detection. This meta-analysis aimed to evaluat...

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Main Authors: Sydney Schwab, Taichiro Nonaka
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2025.1574586/full
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author Sydney Schwab
Taichiro Nonaka
Taichiro Nonaka
author_facet Sydney Schwab
Taichiro Nonaka
Taichiro Nonaka
author_sort Sydney Schwab
collection DOAJ
description ObjectiveColorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, emphasizing the need for noninvasive and reliable diagnostic tools. Circulating microRNAs (miRNAs) have emerged as promising liquid biopsy biomarkers for CRC detection. This meta-analysis aimed to evaluate the diagnostic accuracy of blood- and saliva-derived miRNAs in CRC, assessing their sensitivity, specificity, and overall clinical potential.MethodsA comprehensive literature search was conducted across PubMed, Web of Science, and Scopus to identify relevant studies published between 2004 and 2024. Eligible studies included those that evaluated miRNA expression in plasma, serum, or saliva of CRC patients. A random-effects model was applied to calculate pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC). Heterogeneity was assessed using Cochrane’s Q test and I2 statistics, and risk of bias was evaluated using the QUADAS-2 tool.ResultsA total of 37 studies with 2,775 patients were included in this meta-analysis. The pooled diagnostic performance demonstrated an AUC of 0.87 for combined blood- and saliva-derived miRNAs and 0.86 for blood-derived miRNAs alone, with both categories showing a sensitivity of 0.76 and specificity of 0.83. The diagnostic likelihood ratio (DLR) analysis yielded DLR positive values > 4 and DLR negative values < 0.3, indicating strong discriminatory ability. The DOR was 15.98 for combined blood- and saliva-derived miRNAs and 15.49 for blood-derived miRNAs alone, highlighting their comparable diagnostic potential. These findings suggest that circulating miRNAs serve as reliable biomarkers for CRC detection.ConclusionThis meta-analysis supports the diagnostic utility of circulating miRNAs as noninvasive biomarkers for CRC detection, with saliva-derived miRNAs offering a potential complementary role. Blood-based miRNA analysis demonstrated high diagnostic accuracy, and the integration of saliva-derived miRNAs slightly improved AUC. Future research should focus on standardizing miRNA panels and validation in larger, independent cohorts to facilitate their clinical application in CRC screening and early detection.
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spelling doaj-art-e2fa373c69ad497f890443a758f07fc02025-08-20T02:48:43ZengFrontiers Media S.A.Frontiers in Genetics1664-80212025-07-011610.3389/fgene.2025.15745861574586Circulating miRNAs as liquid biopsy biomarkers for diagnosis in patients with colorectal cancer: a systematic review and meta-analysisSydney Schwab0Taichiro Nonaka1Taichiro Nonaka2School of Medicine, Louisiana State University Health Shreveport, Shreveport, LA, United StatesDepartment of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport, LA, United StatesFeist-Weiller Cancer Center, Louisiana State University Health Shreveport, Shreveport, LA, United StatesObjectiveColorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, emphasizing the need for noninvasive and reliable diagnostic tools. Circulating microRNAs (miRNAs) have emerged as promising liquid biopsy biomarkers for CRC detection. This meta-analysis aimed to evaluate the diagnostic accuracy of blood- and saliva-derived miRNAs in CRC, assessing their sensitivity, specificity, and overall clinical potential.MethodsA comprehensive literature search was conducted across PubMed, Web of Science, and Scopus to identify relevant studies published between 2004 and 2024. Eligible studies included those that evaluated miRNA expression in plasma, serum, or saliva of CRC patients. A random-effects model was applied to calculate pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC). Heterogeneity was assessed using Cochrane’s Q test and I2 statistics, and risk of bias was evaluated using the QUADAS-2 tool.ResultsA total of 37 studies with 2,775 patients were included in this meta-analysis. The pooled diagnostic performance demonstrated an AUC of 0.87 for combined blood- and saliva-derived miRNAs and 0.86 for blood-derived miRNAs alone, with both categories showing a sensitivity of 0.76 and specificity of 0.83. The diagnostic likelihood ratio (DLR) analysis yielded DLR positive values > 4 and DLR negative values < 0.3, indicating strong discriminatory ability. The DOR was 15.98 for combined blood- and saliva-derived miRNAs and 15.49 for blood-derived miRNAs alone, highlighting their comparable diagnostic potential. These findings suggest that circulating miRNAs serve as reliable biomarkers for CRC detection.ConclusionThis meta-analysis supports the diagnostic utility of circulating miRNAs as noninvasive biomarkers for CRC detection, with saliva-derived miRNAs offering a potential complementary role. Blood-based miRNA analysis demonstrated high diagnostic accuracy, and the integration of saliva-derived miRNAs slightly improved AUC. Future research should focus on standardizing miRNA panels and validation in larger, independent cohorts to facilitate their clinical application in CRC screening and early detection.https://www.frontiersin.org/articles/10.3389/fgene.2025.1574586/fullcolorectal cancerbiomarkercirculating biomarkerliquid biopsysaliva diagnostics
spellingShingle Sydney Schwab
Taichiro Nonaka
Taichiro Nonaka
Circulating miRNAs as liquid biopsy biomarkers for diagnosis in patients with colorectal cancer: a systematic review and meta-analysis
Frontiers in Genetics
colorectal cancer
biomarker
circulating biomarker
liquid biopsy
saliva diagnostics
title Circulating miRNAs as liquid biopsy biomarkers for diagnosis in patients with colorectal cancer: a systematic review and meta-analysis
title_full Circulating miRNAs as liquid biopsy biomarkers for diagnosis in patients with colorectal cancer: a systematic review and meta-analysis
title_fullStr Circulating miRNAs as liquid biopsy biomarkers for diagnosis in patients with colorectal cancer: a systematic review and meta-analysis
title_full_unstemmed Circulating miRNAs as liquid biopsy biomarkers for diagnosis in patients with colorectal cancer: a systematic review and meta-analysis
title_short Circulating miRNAs as liquid biopsy biomarkers for diagnosis in patients with colorectal cancer: a systematic review and meta-analysis
title_sort circulating mirnas as liquid biopsy biomarkers for diagnosis in patients with colorectal cancer a systematic review and meta analysis
topic colorectal cancer
biomarker
circulating biomarker
liquid biopsy
saliva diagnostics
url https://www.frontiersin.org/articles/10.3389/fgene.2025.1574586/full
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AT taichirononaka circulatingmirnasasliquidbiopsybiomarkersfordiagnosisinpatientswithcolorectalcancerasystematicreviewandmetaanalysis