Siglec-10 is associated with survival and natural killer cell dysfunction in hepatocellular carcinoma
Siglec-10 is associated with survival and natural killer cell dysfunction in hepatocellular carcinoma
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Siglec-10 与肝细胞癌的存活和自然杀伤细胞功能障碍相关
DOI：
10.1016/j.jss.2014.09.035
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发表时间：
2015-03-01
影响因子：
2.2
通讯作者：
Wu, Ke
中科院分区：
文献类型：
--
作者：
Zhang, Pei;Lu, Xiaoming;Wu, Ke
背景：Siglec-10与其配体CD 24之间的相互作用选择性地抑制组织损伤引起的免疫应答。然而，Siglec-10和CD 24在人肝细胞癌（HCC）中的性质仍然不清楚。方法：采用流式细胞术检测肝癌组织及癌旁组织中Siglec-10的表达，并分析其在肝癌发生发展中的作用。为了进一步确定Siglec-10表达是否与临床特征和生存期相关，在96例HCC患者中进行了常规免疫组织化学。此外，还评价了Siglec-10在调节自然杀伤（NK）细胞功能障碍中的作用。结果：Siglec-10在HCC中的NK细胞上表达最多（40.7 +/-4.5%）。与周围非肿瘤组织相比，肿瘤组织具有更高的Siglec-10表达（31.0 +/- 1.7%对40.7 +/-4.5%，n = 10，P < 0.05），并且表达与患者生存率呈负相关。与Siglec-10（-）CD 56（+）NK细胞相比，Siglec-10（+）CD 56（+）NK细胞表现出降低的效应器功能，如颗粒和细胞因子表达降低所示。此外，肝癌组织中CD 24（+）CD 45（-）细胞的数量高于癌旁非肿瘤组织（9.4 +/-0.9%vs3.1 +/-0.9%，n = 15，P < 0.05）。结论：这些发现表明Siglec-10与人肝癌中生存率降低和NK细胞功能受损相关。这一过程可能通过CD 24-Siglec-10相互作用发挥作用，这可能代表HCC患者的治疗靶点。(C)2015 Elsevier Inc. All rights reserved.
Background: The interaction between Siglec-10 and its ligand, CD24, selectively represses tissue damage-caused immune responses. However, the nature of Siglec-10 and CD24 in human hepatocellular carcinoma (HCC) is still poorly defined. Hereon, the expression, function, and regulation of CD24 and Siglec-10 in HCC were investigated in the present study.Methods: Flow cytometry was performed to examine the expression of Siglec-10 in HCC tissues and adjacent non-tumor tissues of HCC patients. To further determine whether Siglec-10 expression is associated with the clinical characteristics and survival, conventional immunohistochemistry was performed in 96 HCC patients. Additionally, the role of Siglec-10 in the regulation of natural killer (NK) cell dysfunction was evaluated. Finally, CD24 expression in HCC was also assessed.Results: Siglec-10 was expressed most on NK cells in HCC (40.7 +/- 4.5%). Compared with surrounding non-tumor tissues, tumor tissues had higher Siglec-10 expression (31.0 +/- 1.7% versus 40.7 +/- 4.5%, n = 10, P < 0.05), and the expression was negatively associated with patient survival. Siglec-10(+)CD56(+)NK cells exhibited reduced effector function, as shown by decreased granules and cytokine expressions compared with Siglec-10(-)CD56(+) NK cells. Moreover, the number of CD24(+)CD45(-) cells in HCC tissues was higher than that in adjacent non-tumor tissues (9.4 +/- 0.9% versus 3.1 +/- 0.9%, n = 15, P < 0.05).Conclusions: These findings suggest that Siglec-10 is associated with decreased survival and impaired NK cell function in human HCC. This process may function via the CD24-Siglec-10 interaction, which may represent a therapeutic target in HCC patients. (C) 2015 Elsevier Inc. All rights reserved.