SERPINA1is a direct estrogen receptor target gene and a predictor of survival in breast cancer patients
Year: 2015
Type: article
Abstract: // Hei Jason Chan 1 , Haiqing Li 2 , Zheng Liu 3 , Yate-Ching Yuan 3 , Joanne Mortimer 4 , Shiuan Chen 1 1 Department of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, California, USA 2 Department of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, California, USA 3 Bioinformatics Core Facility, Beckman Research Institute of the City of Hope, Duarte, California, USA 4 Department of Medical Oncology, Beckman Research Institute of the City of Hope, Duarte, California, USA Correspondence to: Shiuan Chen, e-mail: [email protected] Keywords: estrogen receptor, breast cancer, endocrine resistance, SERPINA1, survival analysis Received: December 19, 2014 Accepted: June 19, 2015 Published: June 29, 2015 ABSTRACT Of all breast cancer patients, about 70% are ER+ and 10% are ER+/HER2+. The ER+/HER2+ patients have a worse outcome compared to ER+/HER2- patients. Currently there is a lack of effective prognosis biomarkers for the prediction of outcome in ER+/HER2+ patients. Genome-wide differences in ER binding between the endocrine-responsive and endocrine-resistant cells were discovered using ChIP-seq, and combined with gene expression microarray data to identify direct ER target genes. These genes were correlated to survival outcome using publicly available breast cancer patient cohorts. We found the expression of the gene SERPINA1 to have a significant predictive value for the overall survival (OS) of ER+ patients in the TCGA cohort, and validated this finding in the Curtis cohort. SERPINA1 also has a significant predictive value for the OS of ER+/HER2+ patients in the TCGA cohort, with validation in the Bild cohort. The expression of SERPINA1 can be suppressed by fulvestrant and HER2 siRNA. Our results indicate that ER is constitutively activated, resulting in an E2-independent ER binding to the SERPINA1 gene and upregulation of SERPINA1 expression. Importantly, results of survival correlation suggests that high expression of SERPINA1 could be predictive for a better clinical outcome of ER+ and ER+/HER2+ patients.
Source: Oncotarget
Institution: Beckman Research Institute
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: diamond
Funder: National Cancer Institute
OpenAlex ID: W1649914760