Abstract
BackgroundFemale breast cancer is frequently diagnosed at a later stage and the leading cause of cancer deaths world-wide. Levels of cell-free circulating microRNAs (miRNAs) can potentially be used as biomarkers to measure disease progression in breast cancer patients in a non-invasive way and are therefore of high clinical value.MethodsUsing quantitative RT-PCR, circulating miRNAs were measured in blood samples collected from disease-free individuals (n = 34), triple-negative breast tumours (TNBC) (n = 36) and luminal tumours (n = 57). In addition to intergroup comparisons, plasma miRNA expression levels of all groups were analyzed against RNASeq data from cancerous breast tissue via The Cancer Genome Atlas (TCGA).ResultsA differential set of 18 miRNAs were identified in the plasma of breast cancer patients and 10 miRNAs were uniquely identified based on ROC analysis. The most striking findings revealed elevated tumor suppressor let-7 miRNA in luminal breast cancer patients, irrespective of subtype, and elevated miR-195 in plasma of TNBC breast cancer patients. In contrast, hsa-miR-195 and let-7 miRNAs were absent from cancerous TCGA tissue and strongly expressed in surrounding non-tumor tissue indicating that cancerous cells may selectively export tumor suppressor hsa-miR-195 and let-7 miRNAs in order to maintain oncogenesis.ConclusionsWhile studies have indicated that the restoration of let-7 and miR-195 may be a potential therapy for cancer, these results suggested that tumor cells may selectively export hsa-miR-195 and let-7 miRNAs thereby neutralizing their potential therapeutic effect. However, in order to facilitate earlier detection of breast cancer, blood based screening of hsa-miR-195 and let-7 may be beneficial in a female patient cohort.
Highlights
Female breast cancer is frequently diagnosed at a later stage and the leading cause of cancer deaths world-wide
Study cohort and clinical samples processing A total of 127 females, disease-free individuals (n = 34), triple-negative breast tumors (TNBC) (n = 36) and patients with luminal tumors (n = 57) were recruited for the study
Differences in circulating miRNAs between breast cancer patients and normal samples Comparative analysis identified an initial set of 18 circulating miRNAs (Table 1), which because of their differential presence between the patient groups and healthy controls, were further examined by cancer type
Summary
Female breast cancer is frequently diagnosed at a later stage and the leading cause of cancer deaths world-wide. Inconsistencies among studies may be due to patient heterogeneity; genetic background, gender age, metabolic status, as well as methodological challenges [19,20,21,22,23,24] such as sample size, the number of miRNAs studied, blood collection practices and isolation methods [22]. Comorbidities such as obesity and diabetes can significantly affect plasma miRNA levels of putative cancer biomarkers [25, 26]. The miRNA detection method used, sample type tested (plasma versus serum), and the use of either spike-in or endogenous controls for normalization are the major determinants of study outcomes, regardless of the pathological condition in assessment [24]
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