Identification of Cell-Free Circulating MicroRNAs for the Detection of Early Breast Cancer and Molecular Subtyping

Abstract

Early detection is crucial for achieving a reduction in breast cancer mortality. Analysis of circulating cell-free microRNAs present in the serum of cancer patients has emerged as a promising new noninvasive biomarker for early detection of tumors and for predicting their molecular classifications. The rationale for this study was to identify subtype-specific molecular profiles of cell-free microRNAs for early detection of breast cancer in serum. Fifty-four early-stage breast cancers with 27 age-matched controls were selected for circulating microRNAs evaluation in the serum. The 54 cases were molecularly classified (luminal A, luminal B, luminal B Her2 positive, Her-2, triple negative). NanoString platform was used for digital detection and quantitation of 800 tagged microRNA probes and comparing the overall differences in serum microRNA expression from breast cancer cases with controls. We identified the 42 most significant (P ≤ 0.05, 1.5-fold) differentially expressed circulating microRNAs in each molecular subtype for further study. Of these microRNAs, 19 were significantly differentially expressed in patients presenting with luminal A, eight in the luminal B, ten in luminal B HER 2 positive, and four in the HER2 enriched subtype. AUC is high with suitable sensitivity and specificity. For the triple negative subtype miR-25-3p had the best accuracy. Predictive analysis of the mRNA targets suggests they encode proteins involved in molecular pathways such as cell adhesion, migration, and proliferation. This study identified subtype-specific molecular profiles of cell-free microRNAs suitable for early detection of breast cancer selected by comparison to the microRNA profile in serum for female controls without apparent risk of breast cancer. This molecular profile should be validated using larger cohort studies to confirm the potential of these miRNA for future use as early detection biomarkers that could avoid unnecessary biopsy in patients with a suspicion of breast cancer.

Plasma miR-1273g-3p acts as a potential biomarker for early Breast Ductal Cancer diagnosis

“…In recent years, there is a great deal of studies demonstrated the genetic association between miRNAs and cancer, including lung cancer (Hu et al 2016) colorectal cancer (Schetter and Harris 2009) and breast cancer (Takahashi et al 2015, Kurozumi et al 2017. Several previous studies have demonstrated the value of plasma/serum miRNA in breast cancer diagnosis (Lagendijk et al 2018, Khodadadi-Jamayran et al 2018, Souza et al 2019. MiR-21 is involved in regulating the expression of multiple tumor suppressor genes, and plays a crucial role in the occurrence and development of a variety of diseases (Folini et al 2010, Peralta-Zaragoza et al 2016.…”

Circulating miRNAs in HER2-Positive and Triple Negative Breast Cancers: Potential Biomarkers and Therapeutic Targets

“…A recent report exhibited a differential expression of exosomal miR-101 and miR-373 in patients with breast cancer and benign breast tumors; exosomal miR-101 serum levels are deregulated in HER2-positive breast cancer in comparison to its levels in healthy women [113]. A recent study also analyzed ci-miRNAs in serum of breast cancer patients to identify subtype-specific molecular profiles of cell-free miRNAs for early detection of breast cancer in serum; the NanoString platform identified the 42 significant differentially expressed ci-mi-RNAs in each molecular subtype [114]. Of these 42, only four ci-miRNAs (ci-miRNAs-548ar-5p, 584-3p, 615-3p and 1283) are expressed in the HER2-positive subtype [114].…”

“…A recent study also analyzed ci-miRNAs in serum of breast cancer patients to identify subtype-specific molecular profiles of cell-free miRNAs for early detection of breast cancer in serum; the NanoString platform identified the 42 significant differentially expressed ci-mi-RNAs in each molecular subtype [114]. Of these 42, only four ci-miRNAs (ci-miRNAs-548ar-5p, 584-3p, 615-3p and 1283) are expressed in the HER2-positive subtype [114].…”

“…Today, with important advances made in genomic profiling more comprehensive screening of genetic signatures and their downstream targets is possible. In this context, a study by Souza et al (2019) using NanoString platform was able to identify and quantify 42 differentially expressed ci-miRNAs in the serum of breast cancer patients [114]. Among these ci-miRNAs, the expression of miRNA-25-3p was elevated in TNBC patient serum in comparison with matched healthy controls [114].…”

“…In this context, a study by Souza et al (2019) using NanoString platform was able to identify and quantify 42 differentially expressed ci-miRNAs in the serum of breast cancer patients [114]. Among these ci-miRNAs, the expression of miRNA-25-3p was elevated in TNBC patient serum in comparison with matched healthy controls [114]. Moreover, it has been revealed that ci-miRNAs-18b, -103, -107 and -652 significantly correlate with tumor recurrence and reduced survival in TNBC patients [126].…”