Background

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.

Methods

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.

Results

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.

Conclusion

KIF18B could be a useful marker for determining the treatment outcomes of immune checkpoint blockers in the context of hepatocellular carcinoma.

中文翻译：

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KIF18B 作为肿瘤微环境的调节剂加速肿瘤进展并引发肝细胞癌的不良预后

背景

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。使用免疫检查点阻滞剂来提高晚期肝细胞癌患者的总体生存率产生了不一致的结果。我们检查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。

方法

进行生物信息学分析以筛选差异表达的基因并鉴定肝细胞癌肿瘤微环境的核心基因。KIF18B 在肝细胞癌细胞系和肿瘤样品中的表达使用蛋白质印迹、定量实时聚合酶链反应和免疫组织化学测定。使用 Cell Counting Kit-8、集落形成、细胞增殖、迁移和侵袭以及异种移植肿瘤测定来评估 KIF18B 的恶性肿瘤促进能力。

结果

KIF18B 被确定为肝细胞癌微环境中的核心基因之一，与浸润性免疫细胞亚型和肿瘤细胞干性显着相关。KIF18B 的上调与较差的临床病理特征和较差的患者预后相关；其下调抑制了肝癌细胞的增殖能力，与体内实验结果一致。KIF18B 的敲低抑制了上皮间质转化，从而降低了肿瘤细胞的迁移和侵袭能力。肺转移模型证实，KIF18B 的下调抑制了体内肝细胞癌细胞的转移。

结论

KIF18B 可能是确定免疫检查点阻滞剂在肝细胞癌背景下治疗结果的有用标志物。