Department of General Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325035, China.
Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, Institute of Tropical Medicine, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325006, China.
J Cancer Res Clin Oncol. 2020 Mar;146(3):555-568. doi: 10.1007/s00432-019-03092-x. Epub 2020 Feb 5.
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.
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.
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.
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.
我们之前发现人巨细胞病毒（HCMV）感染与胃癌（GC）的发展有关。UL111A 在 HCMV 产毒或潜伏感染过程中发挥作用。然而，GC 组织中 UL111A 的表达谱及其与该疾病的关系尚不清楚。
采用 PCR 和嵌套 RT-PCR 检测 71 例 GC 组织中 UL111A 的表达及其在 16 例 UL111A 阳性 GC 样本中的转录物。采用组织微阵列对 620 例 GC 患者进行免疫组织化学评估，评估 GC 患者 UL111A 的表达水平。分析 UL111A 表达水平与临床病理特征和预后的相关性。进一步评估潜伏相关病毒白细胞介素-10（LAcmvIL-10）和 cmvIL-10 的过表达对 GC 细胞增殖、集落形成、迁移和侵袭的影响。
GC 组织中 UL111A 的检出率为 32.4%（23/71），其 mRNA 表达率为 68.75%（11/16）。UL111A 高表达也与 GC 患者总生存和无病生存时间延长有关。TNM II/III 期 GC 患者表达较高水平的 UL111A 可能受益于术后辅助化疗（ACT）。此外，高 UL111A 表达与 CD4+、CD8+T 淋巴细胞和 Foxp3+T 细胞浸润增加有关。体外试验进一步表明，LAcmvIL-10 和 cmvIL-10 的过表达抑制 GC 细胞系的增殖、集落形成、迁移和侵袭。
高 UL111A 表达改变浸润 T 细胞的数量，并与良好的生存相关。因此，UL111A 可作为独立的预后生物标志物，并可能成为 GC 的潜在治疗靶点。
