Abstract
Breast cancer anti-estrogen resistance protein 3 (BCAR3) is involved in anti-estrogen resistance and other important aspects of breast cancer. However, the role of BCAR3 in other solid tumors remains unclear. The relationship between the clinicopathologic characteristics of head and neck squamous cell carcinoma (HNSCC) patients and BCAR3 was analyzed using the Wilcoxon’s signed-rank test and logistic regression. The association between BCAR3 expression and clinicopathologic features and survival was analyzed using Cox regression and the Kaplan–Meier method. In vivo and in vitro assays were performed to validate the effect of BCAR3 on HNSCC growth. BCAR3-related mRNAs were determined by calculating the Pearson’s correlation coefficient based on The Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and gene set enrichment analysis (GSEA) were used to predict the potential functions of BCAR3. BCAR3 expression is overexpressed in HNSCC and was shown to be associated with perineural invasion (PNI) and poor survival. BCAR3 silencing significantly attenuated the proliferation of HNSCC cells, whereas BCAR3 depletion inhibited tumor growth in vitro. GO and KEGG functional enrichment analyses, and GSEA showed that BCAR3 expression in HNSCC was associated with biological processes, such as cell adhesion, actin binding, cadherin binding, and angiogenesis. BCAR3, which promotes HNSCC growth, is associated with perineural invasion and may be a potential molecular prognostic marker of poor survival in HNSCC.
Highlights
Head and neck squamous cell carcinoma (HNSCC), which is derived from the mucosal epithelium in the oral cavity, pharynx, and larynx, is the sixth most common cancer, with ~890,000 new cases and 450,000 deaths per year worldwide [1, 2]
We found that Breast cancer anti-estrogen resistance protein 3 (BCAR3) expression is significantly associated with poor clinical outcomes of HNSCC cancer patients
BCAR3-related mRNAs were analyzed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the results showed that BCAR3 is likely associated with many important biological functions, such focal adhesion and actin regulation
Summary
Head and neck squamous cell carcinoma (HNSCC), which is derived from the mucosal epithelium in the oral cavity, pharynx, and larynx, is the sixth most common cancer, with ~890,000 new cases and 450,000 deaths per year worldwide [1, 2]. Most HNSCC patients are treated with surgery, chemotherapy, radiotherapy, and molecular targeted therapy. Several targeted agents, such as cetuximab (therapeutic antibody that targets epidermal growth factor (EGF) receptor) and pembrolizumab or nivolumab (programmed cell death protein 1 inhibitors), have been approved by the US Food and Drug Administration for HNSCC treatment, overall response rates have been moderate [2]. Unraveling the molecular mechanisms of HNSCC and identifying prognostic biomarkers are still critical, and may provide disease-specific opportunities for therapeutic exploitation
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