Abstract
Stearoyl-CoA desaturase 1 (SCD1) is an essential regulator of fatty acid synthesis. We have previously shown that overexpression of SCD1 increases the growth of breast cancer cell lines. The purpose of this study was to determine the relationship between SCD1 expression level and clinical-pathologic characteristics and survival of patients with breast cancer. Fine-needle aspirates were collected from the primary tumors of 250 patients with stage I–III breast cancer. Demographic and clinical characteristics including patient age, ethnicity, and menopausal status and tumor clinical stage, grade, and subtype were reviewed. SCD1 expression was analyzed using reverse-phase protein arrays. Samples were divided into high or low SCD1 expression levels based on a cut-off determined from martingale residual plots and regression tree analysis. SCD1 levels were significantly higher in tumors from patients >50-years old compared to patients ≤50-years old and were lower in triple-negative (estrogen/progesterone receptor-negative and human epidermal growth factor receptor-2-negative) breast cancers than other tumor subtypes. After adjusting for patient age, tumor subtype, tumor grade, and clinical stage, we found that patients with primary breast cancers expressing high SCD1 levels had significantly shorter relapse-free survival (RFS) (P = 0.0140) and overall survival (OS) (P = 0.039) in multivariable analysis. We conclude that SCD1 expression varies by breast cancer subtype and that high levels of SCD1 expression are associated with significantly shorter RFS and OS in multivariable analysis. Future studies are needed to define the role of SCD1 in the malignant phenotype of breast cancer and to evaluate the potential for SCD1 as a therapeutic target.
Abbreviations
- SCD1:
-
Stearoyl-CoA desaturase 1
- RFS:
-
Relapse-free survival
- OS:
-
Overall survival
- mTOR:
-
Mammalian target of rapamycin
- TN:
-
Triple-negative
- HR+:
-
Hormone receptor-positive
- HER2+:
-
Human epidermal growth factor receptor-2-positive
- FNA:
-
Fine needle aspirate
- FISH:
-
Fluorescent in situ hybridization
- ER:
-
Estrogen receptor
- PR:
-
Progesterone receptor
- RPPA:
-
Reverse phase protein array
- siRNA:
-
Small interfering RNA
- PI3K:
-
Phosphatidylinositol 3-kinase
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Acknowledgments
This research was supported in part by the National Cancer Institute T32 CA009599-23 (AH, FMB), the Elsa Pardee Foundation (FMB), Susan G. Komen for the Cure SAC10006 (FMB, KAD) and KG 081694 (AMG, GBM) Stand Up to Cancer Dream Team Translational Research Grant, a Program of the Entertainment Industry Foundation (SU2C-AACR-DT0209) (FMB, AA, AMG, GBM), Society of Surgical Oncology Clinical Investigator Award in Breast Cancer Research (FMB), the Kleberg Center for Molecular Markers at The University of Texas MD Anderson Cancer Center, National Cancer Institute 1K23CA121994-01 (AMG), the Cancer Center Support Grant CCSG P30 CA016672 (KAD), and the National Center for Research Resources Grants 3UL1RR024148 (FMB, KAD) and UL1TR000371 (FMB, AA and KAD).
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The authors declare that they have no conflict of interest.
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Holder, A.M., Gonzalez-Angulo, A.M., Chen, H. et al. High stearoyl-CoA desaturase 1 expression is associated with shorter survival in breast cancer patients. Breast Cancer Res Treat 137, 319–327 (2013). https://doi.org/10.1007/s10549-012-2354-4
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DOI: https://doi.org/10.1007/s10549-012-2354-4