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Meta-Analysis
. 2024 Mar 8:15:1362437.
doi: 10.3389/fimmu.2024.1362437. eCollection 2024.

Long noncoding RNAs and circular RNAs as potential diagnostic biomarkers of inflammatory bowel diseases: a systematic review and meta-analysis

Melaku Ashagrie Belete #  1 , Selamyhun Tadesse  2 , Mihret Tilahun  1 , Alemu Gedefie  1 , Agumas Shibabaw  1 , Zewudu Mulatie  1 , Muluken Amare Wudu  3 , Saba Gebremichael  1 , Habtu Debash  1 , Mihreteab Alebachew  1 , Ermiyas Alemayehu #  1
Affiliations
Meta-Analysis

Long noncoding RNAs and circular RNAs as potential diagnostic biomarkers of inflammatory bowel diseases: a systematic review and meta-analysis

Melaku Ashagrie Belete et al. Front Immunol. .

Abstract

Introduction: Inflammatory bowel disease (IBD) poses a growing global burden, necessitating the discovery of reliable biomarkers for early diagnosis. The clinical significance of dysregulated expression of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in diagnosing IBD has not been well established. Thus, our study aimed to investigate the diagnostic value of lncRNAs and circRNAs for IBD based on currently available studies.

Methods: A comprehensive search was carried out in diverse electronic databases, such as PubMed, Embase, Scopus, Science Direct and Wiley Online Library to retrieve articles published until October 30, 2023. Stata 17.0 software was employed to determine pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), and area under the curve (AUC). Heterogeneity, subgroup analysis, and meta-regression were explored, and publication bias was assessed using Deeks' funnel plot. Fagan's nomogram and likelihood ratio scattergram were employed to evaluate the clinical validity.

Result: A total of 11 articles encompassing 21 studies which involved 1239 IBD patients and 985 healthy controls were investigated. The findings revealed lncRNAs exhibit high level of pooled sensitivity 0.94 (95% CI: 0.87-0.97) and specificity 0.99 (95% CI: 0.89-1.00), along with PLR, NLR, DOR, and AUC values of 64.25 (95% CI: 7.39-558.66), 0.06 (95% CI: 0.03-0.13), 1055.25 (95% CI: 70.61-15770.77), and 0.99 (95% CI: 0.97-0.99), respectively. Conversely, CircRNAs showed moderate accuracy in IBD diagnosis, with sensitivity of 0.68 (95% CI: 0.61-0.73), specificity of 0.73 (95% CI: 0.65-0.79), PLR of 2.47 (95% CI: 1.94-3.16), NLR of 0.45 (95% CI: 0.38-0.53), DOR of 5.54 (95% CI: 3.88-7.93), and AUC value of 0.75 (95% CI: 0.71-0.79). Moreover, findings from subgroup analysis depicted heightened diagnostic efficacy when employing lncRNA H19 and a large sample size (≥100), with notable efficacy in diagnosing both ulcerative colitis (UC) and Crohn's disease (CD).

Conclusion: LncRNAs exhibit high diagnostic accuracy in distinguishing patients with IBD from healthy controls signifying their possible use as potential biomarkers, while circRNAs showed moderate diagnostic accuracy. Nevertheless, to validate our findings and confirm the clinical utility of lncRNAs and circRNAs in IBD diagnosis, a large pool of prospective and multi-center studies should be undertaken.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023491840.

Keywords: Crohn’s disease; circRNAs; diagnostic biomarkers; inflammatory bowel disease; lncRNAs; meta-analysis; ulcerative colitis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flow diagram of eligible study selection process for the systematic review and meta-analysis.
Figure 2
Figure 2
Risk of bias assessment of eligible studies using QUADAS-2.
Figure 3
Figure 3
(A) Forest plot of pooled sensitivity and specificity of lncRNAs in diagnosing of IBD. (B) Forest plot of pooled sensitivity and specificity of circRNAs in diagnosing of IBD.
Figure 4
Figure 4
SROC and the 95% confidence contour and 95% prediction contour for lncRNAs (A) and circRNAs (B).
Figure 5
Figure 5
Fagan nomogram and likelihood ratio scattergram for lncRNAs (A) and circRNAs (B).
Figure 6
Figure 6
Scattergram assessing the clinical applicability of lncRNAs (A) and circRNAs (B) for diagnosing IBD.
Figure 7
Figure 7
Meta-regression analysis for sensitivity and specificity of lncRNAs (A) and circRNAs (B).
Figure 8
Figure 8
Sensitivity analysis of included studies for lncRNAs (A) and circRNAs (B).
Figure 9
Figure 9
Deek’s funnel plot of publication bias analysis for lncRNAs (A) and circRNAs (B).
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