Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430077, China.
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Int J Biochem Cell Biol. 2021 Aug;137:106037. doi: 10.1016/j.biocel.2021.106037. Epub 2021 Jul 1.
The tumor microenvironment plays an important role in the progression and recurrence of tumors and immunotherapy outcomes. The use of immune checkpoint blockers to improve the overall survival rate of patients with advanced hepatocellular carcinoma has yielded inconsistent outcomes. We examined the tumor microenvironment-related genes for their clinical significance and biological functions in hepatocellular carcinoma.
Bioinformatic analysis was performed to screen the differentially expressed genes and to identify the core gene of the tumor microenvironment in hepatocellular carcinoma. The expression of KIF18B in hepatocellular carcinoma cell lines and tumor samples was determined using western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. The malignancy-promoting ability of KIF18B was evaluated using Cell Counting Kit-8, colony formation, cell proliferation, migration and invasion, and xenograft tumor assays.
KIF18B was identified as one of the core genes in the hepatocellular carcinoma microenvironment and was significantly associated with infiltrating immune cell subtypes and tumor cell stemness. Upregulation of KIF18B was associated with poor clinicopathological characteristics and poor patient outcomes; its downregulation inhibited the proliferation ability of hepatocellular carcinoma cells, which was consistent with the findings of in vivo experiments. Knockdown of KIF18B inhibited epithelial-mesenchymal transition which reduced the migration and invasion abilities of tumor cells. A pulmonary metastasis model confirmed that the downregulation of KIF18B inhibited hepatocellular carcinoma cell metastasis in vivo.
KIF18B could be a useful marker for determining the treatment outcomes of immune checkpoint blockers in the context of hepatocellular carcinoma.
肿瘤微环境在肿瘤的进展和复发以及免疫治疗结果中起着重要作用。使用免疫检查点抑制剂提高晚期肝细胞癌患者的总生存率的效果不一致。我们研究了肿瘤微环境相关基因在肝细胞癌中的临床意义和生物学功能。
采用生物信息学分析筛选差异表达基因，并鉴定肝细胞癌肿瘤微环境的核心基因。采用 Western blot、实时定量聚合酶链反应和免疫组织化学检测 KIF18B 在肝细胞癌细胞系和肿瘤样本中的表达。通过细胞计数试剂盒-8、集落形成、细胞增殖、迁移和侵袭以及异种移植肿瘤实验评估 KIF18B 的促癌能力。
KIF18B 被鉴定为肝细胞癌微环境中的核心基因之一，与浸润免疫细胞亚型和肿瘤细胞干性显著相关。KIF18B 的上调与不良的临床病理特征和患者预后不良相关；其下调抑制了肝细胞癌细胞的增殖能力，与体内实验结果一致。敲低 KIF18B 抑制了上皮-间充质转化，降低了肿瘤细胞的迁移和侵袭能力。肺部转移模型证实，下调 KIF18B 抑制了体内肝细胞癌细胞的转移。
KIF18B 可能是预测肝细胞癌免疫检查点抑制剂治疗效果的有用标志物。
