microRNAs as novel diagnostic biomarkers in endometriosis patients: a systematic review and meta-analysis

ABSTRACT

Objective

To investigate whether miRNAs have a remarkable pooled diagnostic accuracy, sensitivity, and specificity as noninvasive biomarkers to distinguish endometriosis patients from non-endometriosis women.

Methods

A comprehensive literature search of PubMed, Embase, and ProQuest was performed through February 21, 2021 to find relevant studies. Two reviewers independently screened each article, and discrepancies were resolved by consensus. Deeks’ funnel plot asymmetry test was performed to assess the publication bias of included studies. The STATA software and RevMan 5.4 were used for data analysis and quality assessment, respectively.

Results

The overall quality of the studies was moderate to high. In total 87 datasets were assessed miRNAs’ performance which results in sensitivity: 0.82, specificity: 0.79, DOR: 18, NPV: 0.80, PPV: 0.78, PLR: 3.97, and NLR: 022. We conducted subgroup analyses, which showed panels of miRNAs (DOR: 54) and serum (DOR: 43) as a target tissue was more reliable to utilize as biomarkers. Deeks’ funnel plot showed that there is no publication bias (P-value = 0.25).

Conclusions

Panels of miRNAs differentiate endometriosis patients from non-endometriosis women with high sensitivity and specificity; therefore, it has the potential to use as a noninvasive biomarker.

KEYWORDS:

• Endometriosis
• miRNA
• biomarker
• noninvasive
• meta-analysis

Abbreviations

miR, miRNA, microRNA:	=	micro–Ribonucleic Acid
qRT-PCR:	=	Real-Time Quantitative Reverse Transcription PCR
Spec:	=	Specificity
Sens:	=	Sensitivity
AUC:	=	Area Under the Curve
ROC:	=	Receiver Operating Characteristic
DOR:	=	Diagnostic Odds Ratios
NPV:	=	Negative Predictive Value
PPV:	=	Positive predictive value
PLR:	=	Positive Likelihood Ratio
NLR:	=	Negative Likelihood Ratio
TP:	=	True Positive
FP:	=	False Positive
FN:	=	False Negative
TN:	=	True Negative
LR+:	=	likelihood Ratio Positive
LR−:	=	likelihood Ratio Negative
SD:	=	Standard Deviation
CI:	=	Confidence Interval
FC:	=	Fold Change
QUADAS-2:	=	Quality Assessment of Diagnostic Accuracy Studies 2
BMI:	=	Body Mass Index
CA-125:	=	Cancer Antigen 125

Acknowledgments

Preliminary results and conclusions from this systematic review were presented as poster at the 16^th National Congress of Biochemistry & 7^th International Congress of Biochemistry & Molecular Biology on 9 November 2020. The authors would like to acknowledge colleagues who helped them, especially Farshid Zandsalimi, Parastoo Saberi and Sina Azadnajafabad.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors contributions

M. Majidi Zolbin and Z. Hassannejad conceived and designed the study. S. Yekaninejad drafted the analysis protocol and performed the statistical analysis. S. Emadi Allahyari. and E. Farazi performed the search of databases. A. Bahramy and N. Zafari selected the studies, extracted the data and assessed their quality and risk of bias. N. Zafari and A. Bahramy contributed to the interpretation of data discussed in the manuscript. N. Zafari drafted the original manuscript. S. Yekaninejad, A. Bahramy, M. Majidi Zolbin and Z. Hassannejad revised the manuscript and approved its final version.

Data Availability Statement

Derived data supporting the findings of this study are available from the corresponding author [[email protected]] on request.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

This paper was not funded.