Discovery and function exploration of microRNA-155 as a molecular biomarker for early detection of breast cancer

Abstract

Background: MicroRNA-155 (miR-155) may function as a diagnostic biomarker of breast cancer (BC). Nevertheless, the available evidence is controversial. Therefore, we performed this study to summarize the global predicting role of miR-155 for early detection of BC and preliminarily explore the functional roles of miR-155 in BC.

Methods: We first collected published studies and applied the bivariate meta-analysis model to generate the pooled diagnostic parameters of miR-155 in diagnosing BC such as sensitivity, specificity and area under curve (AUC). Then, we applied function enrichment and protein-protein interactions (PPI) analyses to explore the potential mechanisms of miR-155.

Results: A total of 21 studies were finally included. The results indicated that miR-155 allowed for the discrimination between BC patients and healthy controls with a sensitivity of 0.87 (95% CI 0.78-0.93), specificity of 0.82 (0.72-0.89), and AUC of 0.91 (0.88-0.93). In addition, the overall sensitivity, specificity and AUC for circulating miR-155 were 0.88 (0.76-0.95), 0.83 (0.72-0.90), and 0.92 (0.89-0.94), respectively. Function enrichment analysis revealed several vital ontologies terms and pathways associated with BC occurrence and development. Furthermore, in the PPI network, ten hub genes and two significant modules were identified to be involved in some important pathways associated with the pathogenesis of BC.

Conclusions: We demonstrated that miR-155 has great potential to facilitate accurate BC detection and may serve as a promising diagnostic biomarker for BC. However, well-designed cohort studies and biological experiments should be implemented to confirm the diagnostic value of miR-155 before it can be applied to routine clinical procedures.

Keywords: Biomarker; Breast cancer; Diagnosis; MicroRNA-155.

Fig. 1

The flowchart based on the inclusion and exclusion criteria

Fig. 2

Forest plots of sensitivity and specificity for miR-155 test in breast cancer

Fig. 3

The SROC curves of the pooled individual analyses. a Combined analyses; b outliers excluded; c serum samples; d circulating samples

Fig. 4

Sensitivity analysis results. a Goodness-of-fit; b bivariate normality; c influence analysis; d outlier detection

Fig. 5

The publication bias of all included studies

Fig. 6

Top 10 of the most significantly enriched GO terms. a Biological process; b cellular component; c molecular function. GO, Gene Ontology

Fig. 7

Significantly enriched KEGG pathway. a Top 20 pathways enriched by all the targets of miR-155; b top 20 pathways enriched by the ten hub genes

Fig. 8

The prolactin pathway. The positions in which the target genes of miR-155 cause action are shown with red stars

Fig. 9

PPI network analysis results. PPI, protein–protein interaction

Fig. 10

Module analysis from the protein–protein interaction network. a, b Top two modules extracted from the PPI network; c, d pathway enrichment analysis of the genes in the top two modules