B7 homolog 6 (B7‐H6), a new member of the B7 family, is identified as an activating ligand for cytotoxicity triggering receptor 3 (NKp30) expressing on natural killer cells. The purpose of this study was to investigate the clinical significance of B7‐H6 in hepatocellular carcinoma (HCC). We evaluated B7‐H6 expression by immunohistochemistry in a cohort of 90 HCC tumors with clinical follow‐up, the potential relationship between the B7‐H6 expression and the clinicopathological characteristics of HCC patients was also analyzed. Stable B7‐H6 knockdown in hepatoma cell line was established to explore the function and mechanism of B7‐H6 in HCC. This study showed that high expression of B7‐H6 was significantly associated with smaller tumor size, single tumor number in HCC, but no significant association was found between B7‐H6 overexpression and other clinicopathological parameters. Moreover, Kaplan–Meier survival analysis showed that high expression of B7‐H6 was significantly correlated with better survival of HCC patients. Knockdown of B7‐H6 inhibited tumor cell proliferation and induced cell apoptosis. However, it also impaired the sensitivity of tumor cells to NK‐mediated lysis together with significantly decreased degranulation and IFN‐γ release of NK cells. These results indicated that B7‐H6 has a dual role in HCC. It could be an independent indicator for better survival of HCC and maybe a potential target for future cancer treatment.

中文翻译：

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B7-H6作为肝细胞癌新的预后标志物的双重作用

B7同源物6（B7-H6）是B7家族的新成员，被确定为在自然杀伤细胞上表达的细胞毒性触发受体3（NKp30）的激活配体。本研究的目的是研究B7-H6在肝细胞癌（HCC）中的临床意义。我们通过免疫组化方法对90例HCC肿瘤患者中的B7-H6表达进行了临床随访，并分析了B7-H6表达与HCC患者临床病理特征之间的潜在关系。建立了稳定的肝癌细胞系中的B7-H6敲低基因，以探索B7-H6在肝癌中的功能和机制。这项研究表明，B7-H6的高表达与HCC中较小的肿瘤大小，单个肿瘤数目显着相关，但在B7-H6过表达与其他临床病理参数之间未发现明显关联。此外，Kaplan–Meier生存分析表明，B7-H6的高表达与肝癌患者更好的生存率显着相关。抑制B7-H6抑制肿瘤细胞增殖并诱导细胞凋亡。但是，它也损害了肿瘤细胞对NK介导的裂解的敏感性，并显着降低了NK细胞的脱粒和IFN-γ释放。这些结果表明，B7-H6在肝癌中起双重作用。它可能是肝癌更好生存的独立指标，并且可能是未来癌症治疗的潜在目标。抑制B7-H6抑制肿瘤细胞增殖并诱导细胞凋亡。但是，它也损害了肿瘤细胞对NK介导的裂解的敏感性，并显着降低了NK细胞的脱粒和IFN-γ释放。这些结果表明，B7-H6在肝癌中起双重作用。它可能是肝癌更好生存的独立指标，并且可能是未来癌症治疗的潜在目标。抑制B7-H6抑制肿瘤细胞增殖并诱导细胞凋亡。但是，它也损害了肿瘤细胞对NK介导的裂解的敏感性，并显着降低了NK细胞的脱粒和IFN-γ释放。这些结果表明，B7-H6在肝癌中起双重作用。它可能是肝癌更好生存的独立指标，并且可能是未来癌症治疗的潜在目标。