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Meta-Analysis
. 2023 May 22;13(5):871.
doi: 10.3390/biom13050871.

Circulating microRNAs for Early Diagnosis of Ovarian Cancer: A Systematic Review and Meta-Analysis

Nanna Lond Skov Frisk  1   2 , Anja Elaine Sørensen  1 , Ole Birger Vesterager Pedersen  2   3 , Louise Torp Dalgaard  1
Affiliations
Meta-Analysis

Circulating microRNAs for Early Diagnosis of Ovarian Cancer: A Systematic Review and Meta-Analysis

Nanna Lond Skov Frisk et al. Biomolecules. .

Abstract

In this study, we conducted a systematic review and meta-analysis to summarize and evaluate the global research potential of different circulating miRNAs as an early diagnostic biomarker for OC. A systematic literature search for relevant studies was conducted in June 2020 and followed up in November 2021. The search was conducted in English databases (PubMed, ScienceDirect). The primary search resulted in a total of 1887 articles, which were screened according to the prior established inclusion and exclusion criteria. We identified 44 relevant studies, of which 22 were eligible for the quantitative meta-analysis. Statistical analysis was performed using the Meta-package in Rstudio. Standardized mean differences (SMD) of relative levels between control subjects and OC patients were used to evaluate the differential expression. All studies were quality evaluated using a Newcastle-Ottawa Scale. Based on the meta-analysis, nine miRNAs were identified as dysregulated in OC patients compared to controls. Nine were upregulated in OC patients compared to controls (miR-21, -125, -141, -145, -205, -328, -200a, -200b, -200c). Furthermore, miR-26, -93, -106 and -200a were analyzed, but did not present an overall significant difference between OC patients and controls. These observations should be considered when performing future studies of circulating miRNAs in relation to OC: sufficient size of clinical cohorts, development of consensus guidelines for circulating miRNA measurements, and coverage of previously reported miRNAs.

Keywords: biomarker; diagnostics; meta-analysis; miR-106; miR-141; miR-200b; miR-200c; miR-205; miR-21; miR-26; miR-328; miR-429; microRNA; ovarian cancer; systematic review.

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Conflict of interest statement

Post-doctoral grant from the Danish Diabetes Academy (DDA) supported by the Novo Nordisk Foundation was awarded to AES. The other authors have no conflicting interests to declare.

Figures

Figure 1
Figure 1
The study selection process. The study selection process, from the database search, screening and eligibility evaluation, inclusion for the systematic review and meta-analysis, including the exclusion criteria.
Figure 2
Figure 2
Distribution of miRNAs in included studies. Two hundred sixty-eight miRNAs were identified through the screening of 48 articles. In one study, 83 miRNAs were identified, 22 miRNAs were identified in two studies, 14 miRNAs in three studies, 4 miRNAs in four studies, 3 miRNAs in five studies, and 2 miRNAs in six and seven studies. Additionally, one miRNA in eight and 13 studies. The miRNAs highlighted in bold are the miRNAs that were included in the meta-analysis.
Figure 3
Figure 3
Summary of pre-analytical factors in the included studies. Summary of difference in the methodology used for processing samples and RNA extraction. ND, not defined in the study.
Figure 4
Figure 4
Meta-analysis of studies investigating miR-145-5p, -205-5p, -21-5p, -328-5p, -125-5p, -93-5p, -26-5p, and -106-5p. (A) Forest plot for miR-145-5p, the efficiency for miR-145-5p to distinguish between OC pts and controls. (B) Forest plot for miR-205-5p. (C) Forest plot for miR-21-5p. (D) Forest plot for miR-328-5p. (E) Forest plot for miR-125-5p. (F) Forest plot for miR-93-5p. (G) Forest plot for miR-26-5p. (H) Forest plot for miR-106-5p. CI, confidence interval; SD, standard deviation; SMD, standardized mean difference. *, Data extracted using web plot digitizer.
Figure 5
Figure 5
Meta-analysis of studies investigating microRNAs belonging to the miR-200 family (miR-141-5p, miR-200a-3p, miR-200b-3p, miR-200c-3p, and miR-429-3p). (A) Forest plot for miR-200c-3p, the efficiency for miR-200-3p c to distinguish between OC pts and controls. (B) Forest plot for miR-141-5p. (C) Forest plot for miR-200b-3p. (D) Forest plot for miR-200a-3p. (E) Forest plot miR-429-3p. CI, confidence interval; SD, standard deviation; SMD, standardized mean difference. *, Data extracted using web plot digitizer.
Figure 6
Figure 6
Subgroup meta-analysis of studies investigating. (A) Forest plot of a subgroup for serum based miR-200c-3p studies, the efficiency for miR-200c-3p to distinguish between OC pts and controls. (B) Forest plot of a subgroup for plasma based miR-205-5p studies. (C) Forest plot of a subgroup for plasma based miR-200c-3p studies. (D) Forest plot of a subgroup for plasma based miR-200a-3p studies. CI, confidence interval; SD, standard deviation; SMD, standardized mean difference. S, serum. P, plasma. *, Data extracted using web plot digitizer.
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