GSE68085
Next generation sequencing profiling identifies miR-574-3p and miR-660-5p as potential novel prognostic markers for breast cancer
Prognostication of Breast Cancer (BC) relies largely on traditional markers such as hormone or growth factors but due to their suboptimal specificities, it is challenging to identify the subset of patients who are likely to undergo recurrence and markers of higher specificity are sought to guide therapies. MicroRNAs (miRNAs) are small non-coding RNAs which function as post-transcriptional regulators of gene expression and have shown promise as potential prognostic markers in several cancer types including BC. In our study, we sequenced 104 breast tumor tissue samples and 11 apparently healthy normal breast tissues for miRNAs. Two widely used approaches were adopted to identify prognostic markers – Case-control and Case-only. For both the approaches, Cox-proportional hazards regression model and risk score analysis was performed to identify miRNA signature independent of potential confounders. Representative miRNAs were validated using qRT-PCR. Gene ontology terms were identified for miRNAs significant in survival analysis. A total of 1,423 miRNAs were captured from the tissues, of which 126 were retained with predetermined criteria for good read counts. In the case-control approach, 80 miRNAs were differentially expressed, from which four and two miRNAs were significant for OS and RFS respectively. In the case-only approach, from 147 miRNAs, 11 and four miRNAs were significant for OS and RFS respectively, in which miR-574-3p and miR-660-5p were novel and were not previously found to be associated with BC prognosis.  Multivariate Cox analysis indicated that the risk scores calculated in both the approaches were potential independent prognostic factors for BC. Targets for the identified miRNAs were enriched for cell proliferation, invasion and migration. Overall design: Identification of miRNAs as prognostic markers for breast cancer