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Novel Predictors of Breast Cancer Survival Derived from miRNA Activity Analysis
- Source :
- Clinical Cancer Research. 24:581-591
- Publication Year :
- 2018
- Publisher :
- American Association for Cancer Research (AACR), 2018.
-
Abstract
- Purpose: Breast cancer is among the leading causes of cancer-related death; discovery of novel prognostic markers is needed to improve outcomes. Combining systems biology and epidemiology, we investigated miRNA-associated genes and breast cancer survival in a well-characterized population-based study. Experimental Design: A recently developed algorithm, ActMiR, was used to identify key miRNA “activities” corresponding to target gene degradation, which were predictive of breast cancer mortality in published databases. We profiled miRNA-associated genes in tumors from our well-characterized population-based cohort of 606 women with first primary breast cancer. Cox proportional hazards models were used to estimate HRs and 95% confidence intervals (CI), after 15+ years of follow-up with 119 breast cancer–specific deaths. Results: miR-500a activity was identified as a key miRNA for estrogen receptor–positive breast cancer mortality using public databases. From a panel of 161 miR-500a–associated genes profiled, 73 were significantly associated with breast cancer–specific mortality (FDR < 0.05) in our population, among which two clusters were observed to have opposing directions of association. For example, high level of SUSD3 was associated with reduced breast cancer–specific mortality (HR = 0.3; 95% CI, 0.2–0.4), whereas the opposite was observed for TPX2 (HR = 2.7; 95% CI, 1.8–3.9). Most importantly, we identified set of genes for which associations with breast cancer–specific mortality were independent of known prognostic factors, including hormone receptor status and PAM50–derived risk-of-recurrence scores. These results are validated in independent datasets. Conclusions: We identified novel markers that may improve prognostic efficiency while shedding light on molecular mechanisms of breast cancer progression. Clin Cancer Res; 24(3); 581–91. ©2017 AACR.
- Subjects :
- 0301 basic medicine
Oncology
Cancer Research
medicine.medical_specialty
Population
Breast Neoplasms
Article
03 medical and health sciences
0302 clinical medicine
Breast cancer
Internal medicine
Epidemiology
Biomarkers, Tumor
medicine
Humans
education
education.field_of_study
Proportional hazards model
business.industry
Gene Expression Profiling
Computational Biology
Cancer
Prognosis
medicine.disease
Confidence interval
Gene Expression Regulation, Neoplastic
Gene expression profiling
MicroRNAs
030104 developmental biology
ROC Curve
Receptors, Estrogen
030220 oncology & carcinogenesis
Cohort
Female
Receptors, Progesterone
Transcriptome
business
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 24
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....c44370249c18d8bdb01f9cd3232a7113