may serve as a critical gene in the immune microenvironment of breast cancer.

Background: Breast cancer (BC), a very heterogeneous systemic disease, is the most frequently seen malignancy in women, especially in some developed countries or regions. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and Ki67 have been extensively used to predict the clinical outcome, but it is still a hotspot to search for more predictive prognostic markers. Ankyrin repeat and death domain containing 1A (ANKDD1A), which contains nine ankyrin repeats, has been discovered to play a role of tumor suppressor in glioblastoma multiforme (GBM). However, its role in BC remains unknown so far.

Methods: ANKDD1A expression and clinical information of BC were extracted from the TCGA dataset. Then, the ANKDD1A expression level was explored in BC from different perspectives, including clinical stage, molecular subtype, histology type and immune microenvironment. Afterwards, functional enrichment analysis of ANKDD1A co-expressed genes was carried out to estimate the role of ANKDD1A in BC, and the methylation status of ANKDD1A was evaluated by MEXPRESS. In addition, the correlation of ANKDD1A with immunocytes was explored, and survival analysis was carried out to evaluate the prognostic value of ANKDD1A in BC.

Results: ANKDD1A decreased in BC compared with the para-cancerous tissues. Additionally, ANKDD1A was up-regulated in early-stage BC, ER negative group, infiltrating lobular carcinoma, and the normal subtype in BC molecular subtypes. According to functional enrichment analysis, ANKDD1A co-expressed genes were mainly involved in the immune process. Also, our results revealed that ANKDD1A was tightly associated with T cells. Survival analysis suggested that, patients with higher ANKDD1A expression had more favorable prognosis than those with lower ANKDD1A expression.

Conclusions: ANKDD1A may serve as a critical gene in the pathogenesis of BC and the immune microenvironment of BC tissues.