A nine-miRNA signature as a potential diagnostic marker for breast carcinoma: An integrated study of 1,110 cases

Abstract

Growing evidence indicates that microRNAs (miRNAs) play critical roles in the initiation and progression of breast carcinoma (BC) and are promising diagnostic biomarkers. In the present study, we aimed to identify a multi-marker miRNA pool with high diagnostic performance for BC. We collected miRNA expression profiles of BC samples and normal breast tissues from The Cancer Genome Atlas (TCGA) and screened differentially expressed miRNAs by conducting two‑sample t-tests and by calculating log2 fold-change (log2FC) ratios. Statistical significance was established at p<0.001 and |log2FC| >1. Then, we generated receiver operating characteristic (ROC) curves, calculated the area under the curve (AUC) with a 95% confidence interval (95% CI), and calculated the diagnostic sensitivity and specificity using MedCalc software. Additionally, we predicted the targets of candidate miRNAs using 10 online databases: TarBase, miRTarBase, TargetScan, TargetMiner, microRNA.org, RNA22, PicTar-vert, miRDB, PITA and PolymiRTS. Target genes that were predicted by at least four algorithms were chosen, and cooperative targets of multiple miRNAs were further selected for GO and KEGG pathway analyses through the DAVID online tool. Eventually, a total of 66 differentially expressed miRNAs were identified after miRNA expression profiles were analyzed in BC and normal breast samples. Of these, we selected nine dysregulated miRNAs as candidate diagnostic markers: seven upregulated miRNAs (hsa-miR-21, hsa-miR-96, hsa-miR-183, hsa-miR‑182, hsa-miR-141, hsa-miR-200a and hsa-miR-429) and two downregulated miRNAs (hsa-miR-139 and hsa-miR‑145). The ROC curve for the combination of these nine differently expressed miRNAs showed extremely high diagnostic accuracy, with an AUC of 0.995 (95% CI, 0.988‑0.999) and diagnostic sensitivity and specificity of 98.7 and 98.9%, respectively. In conclusion, the combination of these nine miRNAs significantly improved the accuracy of breast cancer diagnosis.

Association of miR‐1247‐5p expression with clinicopathological parameters and prognosis in breast cancer

“…In recent study, seven microRNAs (miR-21, miR-96, miR-141, miR-182, miR-183, miR-200a and miR-429) were upregulated and two microRNAs (miR-139 and miR-145) were downregulated in human BC. 24 A systematic review showed that two candidate microRNAs (miR-21 and miR-210) were upregulated and six microRNAs (miR-99a, miR-139-5p, miR-145, miR-195, miR-205 and miR-497) were downregulated in BC tissues comparing with normal tissues. 25 Many research have showed that miR-1247-5p was downregulated in cancer tissues, and it act as a tumour inhibition factor.…”

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

“…This is especially important in cancer, a thoroughly heterogenous disease, where a multimarker approach would be preferable. To this extent, a nine-miRNA multimarker panel for breast carcinoma has already been shown to significantly improve the reliability of breast cancer diagnosis [89].…”

Free Circulating miRNAs Measurement in Clinical Settings

“…As for the classical biomarkers, the combination of multiple miRNAs or the combination of a miRNA with protein biomarkers, may increase the sensitivity and specificity of diagnosis and prediction of the studied condition. In supporting this notion, Xiong and co-workers have recently identified a panel of nine miRNAs allowing the early detection of breast cancer with a high diagnostic accuracy with a sensitivity of 98.70% and a specificity of 98.90% [45]. Seeliger et al identified a set of nine miRNAs (hsa-miR-21, hsa-miR-23a, hsa-miR-24, hsa-miR-93, hsa-miR-100, hsa-miR-122a, hsa-miR-124a, hsa-miR-125b, and hsa-miR-148a) significantly upregulated in serum and six miRNAs (hsa-miR-21, hsa-miR-23a, hsa-miR-24, hsa-miR-25, hsa-miR-100, and hsa-miR-125b) significantly upregulated in bone tissues of patients with osteoporosis fractures compared to patients with non-osteoporotic fractures, with five miRNAs upregulated in both serum and bone tissues.…”