Department of Pathology, Yanbian University College of Medicine, Yanji, China; Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji, China.
Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji, China.
Pathol Res Pract. 2021 Feb;218:153323. doi: 10.1016/j.prp.2020.153323. Epub 2021 Jan 2.
B7-H4 is a unique negative regulator of T cells that is typically significantly overexpressed in various carcinomas and is associated with poor prognosis. However, the effects of B7-H4 expression on epithelial-mesenchymal transition (EMT) and cancer stemness of colorectal cancer (CRC) are not entirely clear. In the present study, we used tissue samples from 98 patients with CRC and CRC cell lines to determine the clinicopathological significance of B7-H4 in CRC and its effects on CRC stemness. We performed immunohistochemical staining; immunofluorescence imaging; western blotting; and tumor sphere formation, wound healing, transwell migration, and in vivo tumorigenesis assays. B7-H4 expression was upregulated in CRC tissues and was associated with lymph node metastasis, distant metastasis, clinical stage, a shorter overall survival rate, and disease-free survival rate. Cox regression analyses indicated that B7-H4 is an independent poor prognostic factor for CRC. In addition, B7-H4 expression was correlated with the expression of EMT-related proteins and cancer stemness-related proteins. Moreover, immunohistochemical and immunofluorescence analyses revealed that B7-H4 was correlated with CD133 and CD44 expression levels in both CRC tissues and HT29 and HCT116 cell lines. Conversely, B7-H4 knockdown downregulated the expression of EMT- and cancer stemness-related proteins, while inhibiting tumor spheroid formation, cell migration, and invasion of CRC cell lines. These results indicate that B7-H4 can promote EMT and may be a novel stem cell marker, suggesting its potential as a prognostic biomarker for CRC.
B7-H4 是 T 细胞的一种独特的负性调节剂，通常在各种癌中显著过表达，并与不良预后相关。然而，B7-H4 表达对结直肠癌（CRC）上皮-间充质转化（EMT）和癌症干性的影响尚不完全清楚。在本研究中，我们使用了 98 例 CRC 患者和 CRC 细胞系的组织样本，以确定 B7-H4 在 CRC 中的临床病理意义及其对 CRC 干性的影响。我们进行了免疫组织化学染色；免疫荧光成像；western blot；以及肿瘤球形成、划痕愈合、Transwell 迁移和体内肿瘤生成实验。B7-H4 在 CRC 组织中表达上调，并与淋巴结转移、远处转移、临床分期、总生存率和无病生存率缩短相关。Cox 回归分析表明 B7-H4 是 CRC 的独立不良预后因素。此外，B7-H4 表达与 EMT 相关蛋白和癌症干性相关蛋白的表达相关。此外，免疫组织化学和免疫荧光分析显示，B7-H4 与 CRC 组织和 HT29 和 HCT116 细胞系中的 CD133 和 CD44 表达水平相关。相反，B7-H4 敲低下调了 EMT 和癌症干性相关蛋白的表达，同时抑制了 CRC 细胞系的肿瘤球形成、细胞迁移和侵袭。这些结果表明，B7-H4 可以促进 EMT，并且可能是一种新的干细胞标志物，提示其作为 CRC 预后生物标志物的潜力。
