Overexpression of the human cytomegalovirus UL111A is correlated with favorable survival of patients with gastric cancer and changes T-cell infiltration and suppresses carcinogenesis

Abstract

Purpose We previously found that human cytomegalovirus (HCMV) infection is associated with gastric cancer (GC) development. UL111A plays a role during HCMV productive or latent infection. However, UL111A expression profiles in GC tissues and their relationship with this disease are unknown. Methods PCR and nested RT-PCR were performed to verify UL111A expression in 71 GC tissues and its transcripts in 16 UL111A-positive GC samples. UL111A expression levels in GC patients were evaluated by immunohistochemistry on a tissue microarray for 620 GC patients. The correlations among UL111A expression levels, clinicopathological characteristics, and prognosis were analyzed. Further, the effects of overexpression of latency-associated viral interleukin-10 (LAcmvIL-10) and cmvIL-10 on GC cell proliferation, colony formation, migration, and invasion were assessed. Results The UL111A detection rate in GC tissues was 32.4% (23/71) and that of its mRNA expression was 68.75% (11/16). High expression of UL111A was also related to better overall and disease-free survival in GC patients. GC patients with TNM II/III stage expressing higher UL111A levels might benefit from adjuvant chemotherapy (ACT) after surgery. Moreover, high UL111A expression was also associated with increased CD4+ , CD8+ T-lymphocyte and Foxp3+ T-cell infiltration. In vitro assays further demonstrated that LAcmvIL-10 and cmvIL-10 overexpression inhibits GC cell line proliferation, colony formation, migration, and invasion. Conclusions High UL111A expression changes the number of infiltrating T cells and is associated with favorable survival. Therefore, UL111A could be used as an independent prognostic biomarker and might be a potential therapeutic target for GC.

Functional Profile of Human Cytomegalovirus Genes and Their Associated Diseases: A Review

“…et al, 2015;Wang H.W. et al, 2016;Wang Z. et al, 2016;Arcangeletti et al, 2018;Dennis et al, 2018;Guo et al, 2018;Moussawi et al, 2018;Song et al, 2018;Alston and Dix, 2019;Liu et al, 2020; Figure 2). In immunocompromised individuals, including those with acquired immunodeficiency syndrome (AIDS), transplant recipients, and developing fetuses, the incidence of HCMV infection and mortality are elevated (Crough and Khanna, 2009;Nogalski et al, 2014).…”

“…Meanwhile, US33 activates the proliferation and angiogenesis and inflammatory signaling pathways in glioblastoma cells (Heukers et al, 2018;van Senten et al, 2019). UL111A affects the survival time of gastric carcinoma patients by altering the number of infiltrating T cells (Liu et al, 2020).…”

“…The overexpression of the UL111A protein may result in the recruitment of multiple infiltrating T cells, thereby inhibiting the growth and invasion of gastric cancer cells. Therefore, UL111A may be another potential therapeutic target (Liu et al, 2020; Figure 3C).…”

“…Frequent and active CMV infection plays a vital role in the induction and acceleration of chronic inflammatory reactions in the aortas of patients with inflammatory abdominal aortic aneurysm ( Lindholt and Shi, 2006 ; Liu et al, 2020 ). By aggravating the apoptosis of endothelial cells induced by oxidized low-density lipoprotein, mi R-US25-1 may promote atherosclerosis ( Fan et al, 2014 ).…”

“…et al, 2015 ; Wang H.W. et al, 2016 ; Wang Z. et al, 2016 ; Dennis et al, 2018 ; Guo et al, 2018 ; Moussawi et al, 2018 ; Song et al, 2018 ; Alston and Dix, 2019 ; Liu et al, 2020 ). The roles of HCMV genes in the occurrence and development of diseases have been previously described ( Schleiss, 2011 ).…”