Judith C Sporn1, Eriko Katsuta1, Li Yan2, Kazuaki Takabe3. 1. Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York. 2. Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York. 3. Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York; Department of Surgery, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, The State University of New York, Buffalo, New York; Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo, Japan; Department of Surgery, Yokohama City University, Yokohama, Japan; Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan; Department of Breast Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan. Electronic address: kazuaki.takabe@roswellpark.org.
Abstract
BACKGROUND: MicroRNA-9 (miR-9) was found to play an important role in a variety of different cancers and can adopt either tumor suppressor or oncogenic activity. Most studies have suggested an oncogenic role in breast cancer. We were interested in the relationship of miR-9 expression and survival in breast cancer and hypothesized that high expression of miR-9 was associated with worse prognosis in breast cancer patients. MATERIALS AND METHODS: We utilized The Cancer Genome Atlas containing genetic and molecular data, clinical profiles, and survival information for 985 breast cancers. Survival analysis was performed comparing a group with low expression of miR-9 to a group with high expression. Expression of miR-9 was compared based on clinicopathological parameters. Gene set enrichment analysis was performed between the miR-9 high- and low-expression groups within the estrogen receptor (ER)-positive cohort. RESULTS: Low expression of miR-9 associated significantly with improved overall survival (OS) (P = 0.003). There was no significant difference in miR-9 expression with regard to disease-free survival. Smaller and early-stage tumors were associated with lower miR-9 expression. ER-positive breast cancers had lower levels of miR-9 than ER-negative breast cancers (P < 0.001), and within the ER-positive group, miR-9 expression was significantly associated with OS (P = 0.02). Gene set enrichment analysis showed enrichment of estrogen response genes in the miR-9 low-expression group. CONCLUSIONS: Low miR-9 expression appeared to have a protective effect and was associated with improved OS, smaller tumors, earlier stage, and ER-positive cancers due to enrichment of estrogen response genes.
BACKGROUND: MicroRNA-9 (miR-9) was found to play an important role in a variety of different cancers and can adopt either tumor suppressor or oncogenic activity. Most studies have suggested an oncogenic role in breast cancer. We were interested in the relationship of miR-9 expression and survival in breast cancer and hypothesized that high expression of miR-9 was associated with worse prognosis in breast cancerpatients. MATERIALS AND METHODS: We utilized The Cancer Genome Atlas containing genetic and molecular data, clinical profiles, and survival information for 985 breast cancers. Survival analysis was performed comparing a group with low expression of miR-9 to a group with high expression. Expression of miR-9 was compared based on clinicopathological parameters. Gene set enrichment analysis was performed between the miR-9 high- and low-expression groups within the estrogen receptor (ER)-positive cohort. RESULTS: Low expression of miR-9 associated significantly with improved overall survival (OS) (P = 0.003). There was no significant difference in miR-9 expression with regard to disease-free survival. Smaller and early-stage tumors were associated with lower miR-9 expression. ER-positive breast cancers had lower levels of miR-9 than ER-negative breast cancers (P < 0.001), and within the ER-positive group, miR-9 expression was significantly associated with OS (P = 0.02). Gene set enrichment analysis showed enrichment of estrogen response genes in the miR-9 low-expression group. CONCLUSIONS: Low miR-9 expression appeared to have a protective effect and was associated with improved OS, smaller tumors, earlier stage, and ER-positive cancers due to enrichment of estrogen response genes.