Abstract
BackgroundNuclear receptor subfamily 1, group D, member 1 (NR1D1) is a ligand-regulated nuclear receptor and transcriptional factor. Although recent studies have implicated NR1D1 as a regulator of DNA repair and proliferation in breast cancers, its potential as a therapeutic target for breast cancer has not been assessed in terms of clinical outcomes. Thus, this study aims to analyze NR1D1 expression in breast cancer patients and to evaluate its potential prognostic value.MethodsNR1D1 expression was analyzed by immunohistochemistry using an anti-NR1D1 antibody in 694 breast cancer samples. Survival analyses were performed using the Kaplan–Meier method with the log-rank test to investigate the association of NR1D1 expression with clinical outcome.ResultsOne hundred thirty-nine of these samples exhibited high NR1D1 expression, mostly in the nucleus of breast cancer cells. NR1D1 expression correlated significantly with histological grade and estrogen receptor status. Overall survival (OS) and disease-free survival (DFS) did not correlate significantly with NR1D1 expression in breast cancer patients regardless of whether they had received chemotherapy. Subgroup analysis performed according to molecular subtype of breast cancer showed a significant influence of high NR1D1 expression on OS (P = 0.002) and DFS (P = 0.007) in patients with triple-negative breast cancer (TNBC) treated with chemotherapy.ConclusionsHigh NR1D1 expression level had a favorable impact on OS and DFS in patients with TNBC treated with chemotherapy. NR1D1 should be investigated further as a possible prognostic marker in TNBC patients receiving chemotherapeutic treatment and as a target in the development of chemotherapeutic approaches to treating TNBC.
Highlights
Nuclear receptor subfamily 1, group D, member 1 (NR1D1) is a ligand-regulated nuclear receptor and transcriptional factor
Subgroup analyses according to molecular subtype of breast cancer in patients treated with chemotherapy showed significant influences of high NR1D1 expression on Overall survival (OS) (P = 0.002) and disease-free survival (DFS) (P = 0.007) in triple-negative breast cancer (TNBC) patients who received chemotherapy (Fig. 3). These results suggest that high NR1D1 expression had a favorable effect on OS and DFS in TNBC patients treated with chemotherapy
We found that high NR1D1 expression had a favorable impact on OS and DFS in patients with TNBC treated with chemotherapy
Summary
Nuclear receptor subfamily 1, group D, member 1 (NR1D1) is a ligand-regulated nuclear receptor and transcriptional factor. Recent studies have implicated NR1D1 as a regulator of DNA repair and proliferation in breast cancers, its potential as a therapeutic target for breast cancer has not been assessed in terms of clinical outcomes. This study aims to analyze NR1D1 expression in breast cancer patients and to evaluate its potential prognostic value. Breast cancer is the most common cancer and the main cause of cancer death in women worldwide [1]. It is a diverse and complex disease in terms of its histology and clinical outcomes. The estrogen receptor (ER), progesterone receptor (PR), ERBB2 expression, is the most aggressive subtype with advanced histological grade and poor clinical outcome despite appropriate treatment [3].
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