Integrated Analysis of Key Differentially Expressed Genes Identifies DBN1 as a Predictive Marker of Response to Endocrine Therapy in Luminal Breast Cancer

Abstract

Endocrine therapy is the mainstay of adjuvant treatment for patients with luminal breast cancer. Despite ongoing advances in endocrine therapy to date, a proportion of patients ultimately develop endocrine resistance, resulting in failure of therapy and poor prognosis. Therefore, as part of the growing concept of personalised medicine, the need for identification of predictive markers of endocrine therapy response at an early stage, is recognised. The METABRIC series was used to identify differentially expressed genes (DEGs) in term of response to adjuvant endocrine therapy. Drebrin 1 (DBN1) was identified as a key DEG associated with response to hormone treatment. Next, large, well-characterised cohorts of primary luminal breast cancer with long-term follow-up were assessed at the mRNA and protein levels for the value of DBN1 as a prognostic marker in luminal breast cancer, as well as its potential for predicting the benefit of endocrine therapy. DBN1 positivity was associated with aggressive clinicopathological variables and poor patient outcomes. Importantly, high DBN1 expression predicted relapse patients who were subject to adjuvant endocrine treatment. Our results further demonstrate that DBN1 is an independent prognostic marker in luminal breast cancer. Its association with the response to endocrine therapy and outcome provides evidence for DBN1 as a potential biomarker in luminal breast cancer, particularly for the benefit of endocrine treatment. Further functional investigations into the mechanisms underlying sensitivity to endocrine therapy is required.

Identification and Interaction Analysis of Molecular Markers in Pancreatic Ductal Adenocarcinoma by Bioinformatics and Next-Generation Sequencing Data Analysis

“…KIF2C 43 induces proliferation, migration, and invasion in gastric cancer patients through the MAPK signaling pathway. Drebrin 1 ( DBN1 ) 44 has been reported to be expressed in breast cancer. MAP1B 45 has been reported to be associated with lung cancer progression.…”

Coexpressed Genes That Promote the Infiltration of M2 Macrophages in Melanoma Can Evaluate the Prognosis and Immunotherapy Outcome

“…Some authors used immunohistochemical techniques to measure the overexpression of DBN1 in colorectal cancer tissue lymph nodes and liver metastases in matching tissue sections [ 41 ]. Also, DBN1 is an independent prognostic indicator for luminal breast cancer related to endocrine treatment response and prognosis [ 42 ]. Lyama et al found that, in terms of disease-free survival rate, the prognosis of patients with lung adenocarcinoma with strong DBN1 expression was significantly worse than that of patients with weak DBN1 expression [ 43 ].…”

A novel ferroptosis‑related gene signature for overall survival prediction and immune infiltration in patients with breast cancer

“…In terms of risk factors, DBN1 is an actin-binding protein, which acts as a ferroptosis regulator in pancreatic cancer ( 32 ). High DBN1 expression has been reported to be significantly associated with a poorer prognosis and drug resistance in various types of cancer ( 59 ), including lung adenocarcinoma and breast cancer. Elevated HES1 expression has also been previously reported in multiple types of cancer, including ovarian cancer ( 60 ), non-small cell lung cancer ( 61 ) and breast cancer ( 62 ).…”