Abstract
Simple SummaryNasopharyngeal carcinoma (NPC), Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC), and oral squamous cell carcinoma (OSCC) are epithelial cancers that are associated with EBV infection. However, the gene signatures and common hallmarks associated with EBV infection in EBV-associated epithelial cancers (EBVaCAs) have not been fully elucidated. Here, we performed a panel of transcriptome analyses to identify the gene signatures and common hallmarks of these EBVaCAs. Based on the changes in the expression levels of genes in EBV-infected cell lines and tumor tissues, we identified two upregulated genes, SLC26A9 and TMC8, as gene signatures for EBVaCAs. In addition, SLC26A9 and TMC8 are differentially expressed genes (DEGs) in EBV-infected cells, and their expression is highly correlated with the stimulation of genes involved in numerous biological processes and pathways, such as IL6/JAK/STAT3 and TNF-α/NF-κB signaling pathways. Here, we propose SLC26A9 and TMC8 as novel gene signatures. In addition, we propose IL6/JAK/STAT3 and TNF-α/NF-κB signaling pathways as common hallmarks of EBVaCAs.Epstein-Barr virus (EBV) is associated with various types of human malignancies, including nasopharyngeal carcinoma (NPC), EBV-associated gastric carcinoma (EBVaGC), and oral squamous cell carcinoma (OSCC). The present study aimed to identify gene signatures and common signaling pathways that can be used to predict the prognosis of EBV-associated epithelial cancers (EBVaCAs) by performing an integrated bioinformatics analysis of cell lines and tumor tissues. We identified 12 differentially expressed genes (DEGs) in the EBVaCA cell lines. Among them, only four DEGs, including BAMBI, SLC26A9, SGPP2, and TMC8, were significantly upregulated. However, SLC26A9 and TMC8, but not BAMBI and SGPP2, were significantly upregulated in EBV-positive tumor tissues compared to EBV-negative tumor tissues. Next, we identified IL6/JAK/STAT3 and TNF-α/NF-κB signaling pathways as common hallmarks of EBVaCAs. The expression of key genes related to the two hallmarks was upregulated in both EBV-infected cell lines and EBV-positive tumor tissues. These results suggest that SLC26A9 and TMC8 might be gene signatures that can effectively predict the prognosis of EBVaCAs and provide new insights into the molecular mechanisms of EBV-driven epithelial cancers.
Highlights
Epstein-Barr virus (EBV) is a ubiquitous gamma-herpesvirus that infects more than90% of the world’s population
Microarray analysis was performed on EBV-positive oral squamous cell carcinoma (OSCC) cell lines, HSC1-EBV cells and
The RNA sequencing data of EBV-positive and EBV-negative cell lines derived from nasopharyngeal carcinoma (NPC) or gastric cancer (GC) were retrieved from the Gene Expression Omnibus (GEO) dataset
Summary
Epstein-Barr virus (EBV) is a ubiquitous gamma-herpesvirus that infects more than90% of the world’s population. EBV infection establishes lifelong persistence in the human body by infecting various types of cells, including B lymphocytes, T cells, natural killer cells, and epithelial cells. Histological examination of lesion biopsy is the standard method for determining the clinical stage, prognosis, and treatment of cancer, including NPC, gastric cancer (GC), and OSCC [8,9,10]. This procedure is not suitable for the early diagnosis or screening of patients with malignancies because the procedure is invasive and painful. Exploring signature genes and key molecular mechanisms is critical for the early diagnosis and prognostic evaluation of patients with
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