The Human Cytomegalovirus US31 Gene Predicts Favorable Survival and Regulates the Tumor Microenvironment in Gastric Cancer

Abstract

Human cytomegalovirus (HCMV) is an oncogenic virus associated with tumorigenesis. Our previous study revealed that the HCMV US31 gene interacted with NF-κB2 and mediated inflammation through macrophages. However, there are few reports on the role of US31 in gastric cancer (GC). The aim of this study was to investigate the expression of the US31 gene in GC tissue and assess its role in the occurrence and development of GC. US31 expression in 573 cancer tissues was analyzed using immunohistochemistry. Results showed that US31 was significantly associated with tumor size (P = 0.005) and distant metastasis (P < 0.001). Higher US31 expression indicated better overall survival in GC patients. Overexpression of US31 significantly inhibited the proliferation, migration, and invasion of GC cells in vitro (P < 0.05). Furthermore, expression levels of CD4, CD66b, and CD166 were positively correlated with US31, suggesting that it was involved in regulating the tumor immune microenvironment of GC. RNA sequencing, along with quantitative real-time polymerase chain reaction, confirmed that the expression of US31 promoted immune activation and secretion of inflammatory cytokines. Overall, US31 inhibited the malignant phenotype and regulated tumor immune cell infiltration in GC; these results suggest that US31 could be a potential prognostic factor for GC and may open the door for a new immunotherapy strategy.

Possible Role of Cytomegalovirus in Gastric Cancer Development and Recurrent Macrolide-Resistant Campylobacter jejuni Infection in Common Variable Immunodeficiency: A Case Report and Literature Discussion

“…CMV has previously been implicated in causing gastric ulcers [ 45 , 46 ]. Recently, it has been postulated as a possible oncogenic herpesvirus and a risk factor for the development of gastric cancer [ 47 , 48 , 49 ], although it is still a controversial issue for some authors [ 50 ]. We believe that in our reported case, CMV is one of the main drivers of gastric cancer due to its presence at the gastric level in tumor cells.…”

Human Cytomegalovirus Oncoprotection across Diverse Populations, Tumor Histologies, and Age Groups: The Relevance for Prospective Vaccinal Therapy

“…Recently, Ye et al described an association between the highly conserved US31 CMV gene and its role in suppressing tumor proliferation and metastasis [36]. Further manipulation of the tumor microenvironment is managed through the virus' transformative effects on various cellular genes and signaling pathways [37][38][39][40].…”

Insights into the Transcriptome of Human Cytomegalovirus: A Comprehensive Review

“…Induces NF-κB-mediated mono-macrophage inflammation [511]; Activates immune response and regulates tumor immune microenvironment [512] Induces inflammation [511,512] US32 Unknown Unknown…”