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General Features and Novel Gene Signatures That Identify Epstein-Barr Virus-Associated Epithelial Cancers.

ABSTRACT: 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.

SUBMITTER: Heawchaiyaphum C

PROVIDER: S-EPMC8750470 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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General Features and Novel Gene Signatures That Identify Epstein-Barr Virus-Associated Epithelial Cancers.

Heawchaiyaphum Chukkris C Pientong Chamsai C Yoshiyama Hironori H Iizasa Hisashi H Panthong Watcharapong W Ekalaksananan Tipaya T

Cancers 20211222 1

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 expre ...[more]

PMID: 35008199

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Project description:Epstein-Barr virus (EBV) is convincingly associated with gastric cancer, nasopharyngeal carcinoma, and certain lymphomas, but its role in other cancer types remains controversial. To test the hypothesis that there are additional cancer types with high prevalence of EBV, we determined EBV viral expression in all the Cancer Genome Atlas Project (TCGA) mRNA sequencing (mRNA-seq) samples (n = 10,396) from 32 different tumor types. We found that EBV was present in gastric adenocarcinoma and lymphoma, as expected, and was also present in >5% of samples in 10 additional tumor types. For most samples, EBV transcript levels were low, which suggests that EBV was likely present due to infected infiltrating B cells. In order to determine if there was a difference in the B-cell populations, we assembled B-cell receptors for each sample and found B-cell receptor abundance (P ? 1.4 × 10-20) and diversity (P ? 8.3?×?10-27) were significantly higher in EBV-positive samples. Moreover, diversity was independent of B-cell abundance, suggesting that the presence of EBV was associated with an increased and altered B-cell population. IMPORTANCE Around 20% of human cancers are associated with viruses. Epstein-Barr virus (EBV) contributes to gastric cancer, nasopharyngeal carcinoma, and certain lymphomas, but its role in other cancer types remains controversial. We assessed the prevalence of EBV in RNA-seq from 32 tumor types in the Cancer Genome Atlas Project (TCGA) and found EBV to be present in >5% of samples in 12 tumor types. EBV infects epithelial cells and B cells and in B cells causes proliferation. We hypothesized that the low expression of EBV in most of the tumor types was due to infiltration of B cells into the tumor. The increase in B-cell abundance and diversity in subjects where EBV was detected in the tumors strengthens this hypothesis. Overall, we found that EBV was associated with an increased and altered immune response. This result is not evidence of causality, but a potential novel biomarker for tumor immune status.

Dataset Information

General Features and Novel Gene Signatures That Identify Epstein-Barr Virus-Associated Epithelial Cancers.

Publications

General Features and Novel Gene Signatures That Identify Epstein-Barr Virus-Associated Epithelial Cancers.

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