Whole blood microRNAs as potential biomarkers in post-operative early breast cancer patients

Abstract

BackgroundmicroRNAs (miRNAs) are considered promising cancer biomarkers, showing high reliability, sensitivity and stability. Our study aimed to identify associations between whole blood miRNA profiles, presence of circulating tumor cells (CTCs) and clinical outcome in post-operative early breast cancer patients (EBC) to assess the utility of miRNAs as prognostic markers in this setting.MethodA total of 48 post-operative patients, recruited in frame of the SUCCESS A trial, were included in this retrospective study and tested with a panel of 8 miRNAs (miR-10b, −19a, − 21, − 22, −20a, − 127, − 155, −200b). Additional 17 female healthy donors with no previous history of cancer were included in the study as negative controls. Blood samples were collected at different time points (pre-adjuvant therapy, post-adjuvant therapy, 2 years follow up), total RNA was extracted and the relative concentration of each miRNA was measured by quantitative PCR and compared in patients stratified on blood collection time or CTC detection. Furthermore, we compared miRNA profiles of patients, for each time point separately, and healthy donors. CTCs were visualized and quantified with immunocytochemistry analysis. Data were analyzed using non-parametric statistical tests.ResultsIn our experimental system, miR-19a, miR-22 and miR-127 showed the most promising results, differentiating patients at different time points and from healthy controls, while miR-20a, miR-21 and miR-200b did not show any difference among the different groups. miR-10b and miR-155 were never detectable in our experimental system. With respect to patients’ clinical characteristics, we found a significant correlation between miR-200b and lymph node status and between miR-20a and tumor type. Furthermore, miR-127 correlated with the presence of CTCs. Finally, we found a borderline significance between Progression Free Survival and miR-19a levels.ConclusionsThis pilot study suggests that profiling whole blood miRNAs could help to better stratify post-operative EBC patients without any sign of metastasis to prevent later relapse or metastatic events.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4020-7) contains supplementary material, which is available to authorized users.

Upregulation of Circulating MiR-21 Expression as a Potential Biomarker for Therapeutic Monitoring and Clinical Outcome in Breast Cancer

“…Expression levels of circulating miR-21 were not significantly different among different clinical stages and tumor differentiation grades. Other previous studies (Alunni-Fabbroni et al, 2018;Gao et al, 2013) also did not find an association of miR-21 expression with baseline stages and differentiation grades. We presented higher expression of circulating miR-21 in young breast cancer patients (less than 40-year-old) that are commonly associated with aggressive biology and poor prognosis (Anwar et al, 2019).…”

“…We also primarily demonstrated that miR-21 expression decreased significantly after surgery and chemotherapy rendering the potential role as therapeutic monitoring marker. Measuring in breast cancer patient's whole blood, the previous study did not observe different miR-21 expression measured before and after surgery (Alunni-Fabbroni et al, 2018). Alterations of microRNA expression after surgical resection were also not observed in the whole blood of patients with lung cancer (Patnaik et al, 2017).…”

Change of Circulating and Tissue-Based miR-20a in Human Cancers and Associated Prognostic Implication: A Systematic Review and Meta-Analysis

“…It is reported that upregulated miR-20a could promote colorectal cancer growth and progression by inhibiting multiple tumor-suppressive genes such as BIM and Smad4 [14, 48], while in breast cancer, miR-20a achieved inhibitory effect of cancer cell proliferation through directing targeting MAPK1/ERK2, a member of Ras/Raf/ERK pathway [32]. Impressively, existing evidences did not support aberrant circulating miR-20a in patients with breast cancer, cutaneous squamous cell carcinoma, hepatocellular carcinoma, oral squamous cell carcinoma, epithelial ovarian cancer, salivary adenoid cystic carcinoma, gallbladder carcinoma, and alveolar rhabdomyosarcoma compared with normal healthy controls [49]. Only in gastrointestinal tumors, upregulated miR-20a level in both serum/blood and tumorous tissue was confirmed and high expression of both circulating and tumorous miR-20a was associated with an unfavorable outcome.…”

MiR‐202 inhibits cell proliferation, invasion, and migration in breast cancer by targeting ROCK1 gene

“…Based on the results of this research, we recommended miR‐202 as one of the biomarkers for breast cancer management. In addition, some literatures had used blood miRNAs levels as diagnostic tools for breast cancer . Compared with miRNAs levels detection in tumor tissues, blood miRNAs levels detection, and diagnosis would be much faster and more convenient.…”