Abstract
The role of L Antigen Family Member 3 (LAGE3) in breast cancer (BC) has not been sufficiently studied. In this study, we explored the clinical value and biological functions of LAGE3 in BC. Comprehensive analysis of LAGE3 was carried out on The Cancer Genome Atlas, Molecular Taxonomy of Breast Cancer International Consortium and Gene Expression Omnibus datasets. Results showed that LAGE3 expression was higher in BC tissues than in normal breast tissues of public datasets and our local cohort. Moreover, its expression was higher in BC patients with larger tumor size, significant lymph node metastasis, higher tumor grade, and more advanced disease stage. High expression of LAGE3 was correlated with poor prognosis, and LAGE3 could independently predict survival of BC patients. Functional enrichment analysis revealed a correlation between LAGE3 expression and biochemical metabolism and immune-related terms and cancer-related pathways. Analysis of tumor microenvironment indicated that LAGE3 expression was associated with the immune cell infiltration and anti-cancer immunity cycle. LAGE3 expression was higher in triple-negative breast cancer (TNBC) compared to hormone receptor-positive BC, but not HER2-positive subtype. Suppression of LAGE3 expression inhibited the proliferation and induced apoptosis of TNBC cell lines. Besides, the down-regulation of LAGE3 attenuated the migration and invasion but reduced the expression level of epithelial-mesenchymal-transition related proteins in TNBC cell lines. In conclusion, this study demonstrated for the first time that LAGE3 promotes the progression of BC. Therefore, it may be a potential diagnostic and prognostic biomarker, as well as a treatment target for BC.
Highlights
Breast cancer (BC) is the most common malignant disease and the leading cause of cancer death among women worldwide
We demonstrated that L Antigen Family Member 3 (LAGE3) was highly up-regulated in BC tissues compared to normal breast tissues in six public datasets, which contained more than 3,500 patients
When we investigated the correlation between LAGE3 expression and clinicopathological factors in BC, we noticed that the upregulation of LAGE3 was associated with the higher T stage, more metastatic lymph nodes, higher tumor grades, and more advanced disease stages
Summary
Breast cancer (BC) is the most common malignant disease and the leading cause of cancer death among women worldwide. BC is staged based on the TNM (Tumor, Nodes, Metastasis) staging system, all of which characterize the disease, influence the prognosis, and guide. The 5-year survival rates of BC patients with anatomical stages of stage I, IIA, IIB, IIIA, IIIB, and IV are 95, 85, 70, 52, 48, and 18%, respectively [3]. Lymph node metastasis (LNM), and histologic grade were identified as important prognostic factors in patients with BC [4,5,6,7]. Immune checkpoint inhibitors like Atezolizumab (anti-programmed death-ligand 1 antibody) have been approved for the treatment of BC [13]. It is of great value to identify reliable BC-specific biomarkers for diagnosis, prognosis, and targeted therapy
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