Abstract
Background The human antimicrobial peptide defensin beta 1 (DEFB1) has been found to play antimicrobial and anti-inflammatory roles in oral diseases; however, its tumor-regulating role in oral squamous cell carcinoma (OSCC) has not yet been researched by using an integrative bioinformatics approach. Objective To investigate the regulating mechanisms of the DEFB1 gene in OSCC in terms of its expression patterns, prognostic values, biological functions, and implication for tumor immunity. Methods The DEFB1 gene expression pattern and regulatory involvement in OSCC were investigated using publically accessible data from TCGA database. R software tools and public web servers were utilized to conduct statistical analysis of data from cancer and noncancerous samples. Results DEFB1 was found to be significantly downregulated in OSCC tumor samples compared with healthy control oral samples. The DEFB1 gene was found associated with the prognostic outcomes of OSCC, and its upregulation represented better survival outcome. Gene set enrichment analysis (GSEA) results showed that DEFB1-significantly correlated genes were mainly enriched in four signaling pathways mediating the antitumor role of DEFB1 in OSCC, including extracellular matrix-related pathway, RTK/PI3K/AKT/mTOR pathway, keratinization, and cytokine-related pathway. The gene-gene interaction network showed that DEFB1 was closely correlated with several genes, for example, CCR6 (C-C motif chemokine receptor 6), CXCL1 (C-X-C motif chemokine ligand 1), MAP4K2 (mitogen-activated protein kinase kinase kinase kinase 2), PTGER3 (prostaglandin E receptor 3), and MMP7 (matrix metallopeptidase 7). Moreover, DEFB1 was found to be involved in the tumor immunity of OSCC by regulating the function of tumor macrophage cells, mast cells, T cells, and NK cells. Conclusions Given the dysregulation, prognostic value, and tumor progression-related biological pathway alteration, indicating the tumor immune-modulatory role of DEFB1 in OSCC, the DEFB1 gene should be regarded as a potential therapeutic target for treating oral cancer.
Highlights
Antimicrobial peptides (AMPs) are short peptides with cationic charges, which are characterized by a broad spectrum of antibacterial activities and a low degree of resistance [1]
The univariate analysis results showed that four variables were statistically significantly related to the overall survival of oral squamous cell carcinoma (OSCC) patients, while the other variables (e.g., T stage, N stage, M stage, age, gender, race, smoker, clinical stage, alcohol history, histologic grade, lymph node neck dissection, and anatomic neoplasm subdivision) were not shown to be statistically significantly associated with the overall survival of OSCC patients
The multivariate analysis results showed that several variables (T stage, radiation therapy, primary therapy outcome, lymphovascular invasion, and defensin beta 1 (DEFB1) expression) were statistically significantly associated with the overall survival of OSCC patients; the other variables (e.g., N stage, M stage, age, and lymph node neck dissection) were not shown to be associated with the overall survival of OSCC patients
Summary
Antimicrobial peptides (AMPs) are short peptides with cationic charges, which are characterized by a broad spectrum of antibacterial activities and a low degree of resistance [1]. AMPs are well-known because of their function in modulating the immune response and are regarded as critical host defense molecules involved in human innate immunity [3]. Apart from their antibacterial and immune modulatory roles, AMPs have recently attracted considerable attention because of their regulating role in many cancers [4]. To investigate the regulating mechanisms of the DEFB1 gene in OSCC in terms of its expression patterns, prognostic values, biological functions, and implication for tumor immunity. Prognostic value, and tumor progression-related biological pathway alteration, indicating the tumor immune-modulatory role of DEFB1 in OSCC, the DEFB1 gene should be regarded as a potential therapeutic target for treating oral cancer
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