The Second Clinical Medical College of Lanzhou University, Lanzhou, China.
Department of Oncology Surgery, Lanzhou University Second Hospital, Lanzhou, China.
APMIS. 2022 Jul;130(7):371-382. doi: 10.1111/apm.13219. Epub 2022 May 17.
Accurate assessment of the tumour immune microenvironment promotes individualized immunotherapy regimens and screens dominant populations suitable for immunotherapy. Therefore, potential molecular markers were investigated to make an overall assessment of the immune microenvironment status of liver hepatocellular carcinoma (LIHC). In this study, a total of 121 differentially expressed genes (DEGs) were identified, and DEGs were enriched in the epithelial-mesenchymal transition, hypoxia, myogenesis, and p53 pathways. A total of 20 hub genes were selected and a strong correlation was identified between these hub genes and prognosis. The expression of budding uninhibited by benzimidazoles 1 (BUB1) was found to be upregulated in LIHC and was strongly related to immune cells and immune checkpoint molecule expression. Immunohistochemistry (IHC) indicated that BUB1 expression was higher in LIHC tissues than in normal liver tissues. BUB1 knockdown resulted in reduced proliferation and vertical migration ability of LIHC cells, and reduced the expression of phospho-SMAD family member 2 and phospho-SMAD family member 3 proteins. IHC showed that BUB1 expression was accompanied by immune cell infiltration into LIHC tissues. These results suggest that BUB1 may serve as a potential prognostic biomarker for LIHC and as an indicator of its immune status.
准确评估肿瘤免疫微环境可促进个体化免疫治疗方案的制定,并筛选出适合免疫治疗的优势人群。因此,研究人员调查了潜在的分子标志物,以全面评估肝癌(LIHC)的免疫微环境状态。在本研究中,共鉴定出 121 个差异表达基因(DEGs),DEGs 富集在上皮-间充质转化、缺氧、肌生成和 p53 途径中。共选择了 20 个枢纽基因,并发现这些枢纽基因与预后之间存在很强的相关性。发现芽殖抑制蛋白 1(BUB1)在 LIHC 中表达上调,与免疫细胞和免疫检查点分子表达密切相关。免疫组织化学(IHC)表明,BUB1 在 LIHC 组织中的表达高于正常肝组织。BUB1 敲低导致 LIHC 细胞的增殖和垂直迁移能力降低,同时降低磷酸化 SMAD 家族成员 2 和磷酸化 SMAD 家族成员 3 蛋白的表达。IHC 显示 BUB1 的表达伴随着免疫细胞浸润到 LIHC 组织中。这些结果表明,BUB1 可能是 LIHC 的潜在预后生物标志物,也是其免疫状态的指标。