Altered gene expression profile in human gingival keratinocytes treated with Aggregatibacter actinomycetemcomitans and their role in the development of head and neck squamous cell carcinoma.

内容摘要

Periodontal diseases have been associated with several systemic conditions, including certain types of cancer. Chronic inflammation, a characteristic feature of periodontal disease, has been hypothesized to contribute to carcinogenesis and tumor progression. However, the specific relationship between Aggregatibacter actinomycetemcomitans and cancer development remains an area of ongoing research. The aim of the study was to investigate the potential association between A. actinomycetemcomitans, a well-established periodontal pathogen, and the development of head and neck squamous cell carcinoma (HNSCC). Additionally, the objective was to examine differentially expressed genes (DEGs) in A. actinomycetemcomitans-infected human immortalized gingival keratinocytes (HIGKs) and compare their expression in the HNSCC dataset using computational tools. The Gene Expression Omnibus (GEO) dataset GSE9723 was used to retrieve the global gene expression profile of human gingival keratinocytes exposed to A. actinomycetemcomitans. A computational approach was employed using the PANTHER (Protein ANalysis THrough Evolutionary Relationships) Classification System for gene ontology analysis, STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) for network analysis and UALCAN (University of ALabama at Birmingham CANcer data analysis) for gene expression and survival analyses. The GEO2R analysis identified numerous DEGs, of which the top 25 were selected for further evaluation using the HNSCC dataset from The Cancer Genome Atlas (TCGA). Among these genes, DDIT4 and RCE1 demonstrated expression patterns consistent with those observed in A. actinomycetemcomitans-infected HIGKs. Further analysis revealed that patients presenting with elevated DDIT4 and RCE1 expression levels demonstrated a marked reduction in overall survival. The findings suggest that DDIT4 and RCE1 can be considered potential therapeutic targets associated with A. actinomycetemcomitans-mediated induction of head and neck cancers. However, further studies are required to validate these observations.