8 research outputs found
Hsa-miR-375 is a predictor of local control in early stage breast cancer
Background: A long-term analysis by the Early Breast Cancer Trialist Group (EBCTG) revealed a strong correlation between local control and cancer-specific mortality. MicroRNAs (miRs), short (20-25 nucleotides) non-coding RNAs, have been described as prognosticators and predictors for breast cancer in recent years. The aim of the current study was to identify miRs that can predict local control after breast conserving therapy (BCT) in early stage breast cancer. Results: Clinical data of 46 early stage breast cancer patients with local relapse after BCT were selected from the institutional database. These patients were matched to 101 control patients showing identical clinical features but without local relapse. The study was conducted in two steps. (1) In the pilot study, 32 patients (16 relapses versus 16 controls) were screened for the most de-regulated microRNAs (= candidate microRNAs) in a panel of 1250 miRs by microarray technology. Eight miRs were found to be significantly de-regulated. (2) In the validation study, the candidate microRNAs were analyzed in an independent cohort of 115 patients (30 relapses versus 85 controls) with reverse transcription quantitative polymerase chain reaction (RT-qPCR). From these eight candidates, hsa-miR-375 could be validated. Its median fold change was 2.28 (Mann-Whitney U test, corrected p value = 0.008). In the log-rank analysis, high expression levels of hsa-miR-375 correlated with a significantly higher risk of local relapse (p = 0.003). In a multivariate analysis (forward stepwise regression) including established predictors and prognosticators, hsa-miR-375 was the only variable that was able to distinguish the statistical significance between relapse and control groups (raw p value = 0.000195 HR = 0.76, 95 % CI 0.66-0.88;corrected p value = 0.005). Conclusions: Hsa-miR-375 predicts local control in patient with early stage breast cancer, especially in estrogen receptor alpha (ER-alpha)-positive patients. It can therefore serve as an additional molecular marker for treatment choice independently from known predictors and prognosticators. Validation in larger prospective studies is warranted
Additional file 5: Figure S1. of Hsa-miR-375 is a predictor of local control in early stage breast cancer
Study flow-chart. This additional file shows the various steps of the study. (PDF 42.8 kb
Additional file 6: Table S1. of Hsa-miR-375 is a predictor of local control in early stage breast cancer
RT-qPCR target information. This table provides information on the exact sequences of the primers that were used for RT-qPCR including the QiagenâÂË catalog number. (PDF 29.9 kb
Additional file 3: Figure S3. of Hsa-miR-375 is a predictor of local control in early stage breast cancer
Target prediction for hsa-miR-375. The Venn diagram shows the number of predicted targets from TargetScan (blue) http://www.targetscan.org/and PITA (red) http://genie.weizmann.ac.il/pubs/mir07/mir07_data.html; 15 genes were suggested by both algorithms. (PDF 44.5 kb
Additional file 4: Figure S4. of Hsa-miR-375 is a predictor of local control in early stage breast cancer
Predicted targets of hsa-miR-375 and cancer pathways. Gene enrichment analysis of the predicted targets by GeneCoDis3 software (http://genecodis.cnb.csic.es/). RASD1 was assigned to the PI3K-pathway (http://www.pantherdb.org/pathway/). The numbers on the x-axis indicate how many of the 15 âÂÂoverlappingâ genes in Additional file 3: Figure S3 are found in a specific pathway. (PDF 20.2 kb