Show simple item record Krishnan, Preethi Ghosh, Sunita Wang, Bo Li, Dongping Narasimhan, Ashok Berendt, Richard Graham, Kathryn Mackey, John R. Kovalchuk, Olga Damaraju, Sambasivarao 2017-07-12T21:46:33Z 2017-07-12T21:46:33Z 2015
dc.identifier.citation Krishnan, P., Ghosh, S., Wang, B., Dongping, L., Narasimhan, A., Berendt, R. ... Damaraju, S. (2015). Next generation sequencing profiling identifies miR-574-3- and miR-660-5p as potential novel prognostic markers for breast cancer. BMC Genomics, 16, 735. doi:10.1186/s12864-015-1899-0 en_US
dc.description Sherpa Romeo green journal: open access en_US
dc.description.abstract Background: Prognostication of Breast Cancer (BC) relies largely on traditional clinical factors and biomarkers such as hormone or growth factor receptors. Due to their suboptimal specificities, it is challenging to accurately identify the subset of patients who are likely to undergo recurrence and there remains a major need for markers of higher utility to guide therapeutic decisions. MicroRNAs (miRNAs) are small non-coding RNAs that function as post-transcriptional regulators of gene expression and have shown promise as potential prognostic markers in several cancer types including BC. Results: In our study, we sequenced miRNAs from 104 BC samples and 11 apparently healthy normal (reduction mammoplasty) breast tissues. We used Case–control (CC) and Case-only (CO) statistical paradigm to identify prognostic markers. Cox-proportional hazards regression model was employed and risk score analysis was performed to identify miRNA signature independent of potential confounders. Representative miRNAs were validated using qRT-PCR. Gene targets for prognostic miRNAs were identified using in silico predictions and in-house BC transcriptome dataset. Gene ontology terms were identified using DAVID bioinformatics v6.7. A total of 1,423 miRNAs were captured. In the CC approach, 126 miRNAs were retained with predetermined criteria for good read counts, from which 80 miRNAs were differentially expressed. Of these, four and two miRNAs were significant for Overall Survival (OS) and Recurrence Free Survival (RFS), respectively. In the CO approach, from 147 miRNAs retained after filtering, 11 and 4 miRNAs were significant for OS and RFS, respectively. In both the approaches, the risk scores were significant after adjusting for potential confounders. The miRNAs associated with OS identified in our cohort were validated using an external dataset from The Cancer Genome Atlas (TCGA) project. Targets for the identified miRNAs were enriched for cell proliferation, invasion and migration. Conclusions: The study identified twelve non-redundant miRNAs associated with OS and/or RFS. These signatures include those that were reported by others in BC or other cancers. Importantly we report for the first time two new candidate miRNAs (miR-574-3p and miR-660-5p) as promising prognostic markers. Independent validation of signatures (for OS) using an external dataset from TCGA further strengthened the study findings. en_US
dc.language.iso en_US en_US
dc.publisher BioMed Central en_US
dc.subject microRNA en_US
dc.subject Next generation sequencing en_US
dc.subject Breast cancer en_US
dc.subject Prognostic marker en_US
dc.subject miR-574-3p en_US
dc.subject miR-660-5p en_US
dc.subject Reduction mammoplasty en_US
dc.subject Overall survival en_US
dc.subject Recurrence free survival en_US
dc.subject TCGA en_US
dc.title Next generation sequencing profiling identifies miR-574-3p and miR-660-5p as potential novel prognostic markers for breast cancer en_US
dc.type Article en_US
dc.publisher.faculty Arts and Science en_US
dc.publisher.department Department of Biological Sciences en_US
dc.description.peer-review Yes en_US
dc.publisher.institution University of Alberta en_US
dc.publisher.institution Cross Cancer Institute en_US
dc.publisher.institution University of Lethbridge en_US

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