Dear Editor,
We read with great interest the systematic review by Eini et al. [1], synthesizing microRNA biomarker evidence in abdominal aortic aneurysm.
1. Overlapping cohorts behind the most reproducible tissue signals
This review identified miR-21 and miR-146a as the most consistently dysregulated tissue miRNAs, largely based on publications from the same research group spanning 2012 to 2014. Serial reports from one center, potentially drawing on overlapping surgical cohorts, cannot function as independent replications in the way the synthesis implies [2]. A biomarker candidate needs confirmation across genuinely separate patient populations before a clinician treats it as reproducible, and the current narrative risks presenting repeated analyses of a shared sample as convergent evidence from distinct sources [3].
2. Diagnostic AUCs from single small cohorts require a different reading
Several circulating miRNAs have AUC values above 0.9, including figures near 0.98, drawn from single PBMC cohorts without external validation. Near-perfect discrimination from an underpowered, unreplicated dataset more often indicates overfitting than genuine diagnostic separation [4]. Presenting these figures alongside multi-cohort findings, without flagging the instability inherent to single-study point estimates, invites readers to weigh unstable and stable evidence equally when prioritizing candidates for prospective validation [5].
3. Conclusion
Distinguishing genuinely independent replication from repeated analysis of related cohorts and separating stable multi-study AUC estimates from single-cohort outliers would sharpen which circulating and tissue miRNAs merit prioritization in prospective validation studies this field needs.
Ethical approval
Not applicable (commentary on previously published research).
Data availability
No new data were generated or analyzed for this manuscript.
CRediT author statement
V.P. contributed to conceptualization, literature review, manuscript drafting, critical interpretation of the study findings, manuscript revision, and final approval of the version to be submitted.
Generative AI disclosure
Generative AI tools were used solely for language refinement and formatting assistance. All scientific interpretation, critique, and conceptual analysis were independently developed by the author.
Funding
None.
Declaration of competing interests
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.
The authors declare the following financial or non-financial interests which may be considered as potential conflicts of interest.
Acknowledgment
None.
References
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Data Availability Statement
No new data were generated or analyzed for this manuscript.