免疫抑制受体 LILRB1 通过与 SHP1 结合成为肝癌的潜在调控因子。
Immunosuppressive receptor LILRB1 acts as a potential regulator in hepatocellular carcinoma by integrating with SHP1.
机构信息
Shaanxi Key Laboratory of Brain Disorders and School of Basic Medical Science, Xi'an Medical University, Xi'an, Shaanxi, China.
Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi, China.
出版信息
Cancer Biomark. 2020;28(3):309-319. doi: 10.3233/CBM-190940.
BACKGROUND
Immunosuppressive receptor LILRB1 regulates tumors progression by transducing immune inhibitory signals via intracellular immunoreceptor tyrosine-based inhibitory motifs. However, its role in Hepatocellular Carcinoma (HCC) remains vague.
OBJECTIVE
This study is aimed to disclose the association between LILRB1 and HCC.
METHODS
Immunoblotting and qRT-PCR were employed to evaluate the level of LILRB1 in hepatocarcinoma cells. LILRB1-positive cells in tissue array were measured using immunohistochemistry staining. The relation among LILRB1, SHP1 and SHP2 and survival rates were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) and Oncomine database.
RESULTS
LILRB1 was robustly reduced in hepatocarcinoma cells compared to normal cells. Clinically, LILRB1 was significantly higher in 49 of 75 (65%) paired paracarcinoma tissues than that in paired HCC samples. 48 of 75 (64%) HCC subjects in tissue microarray showed low level of LILRB1, compared to 25 of 75 (33%) in paired-adjacent tissues. Oncomine database and GEPIA analysis confirmed that LILRB1 was lower in HCC than normal tissues. Additionally, lowLILRB1 had a significant association with clinicopathological characteristics and Disease Free Survival, but no association with Overall Survival in HCC patients. Mechanismly, positive correlation between LILRB1 and SHP1, but not SHP2 was observed in HCC.
CONCLUSIONS
LILRB1 possibly plays an antitumor effect in hepatocarcinoma cells by integrating SHP1, providing evidence that LILRB1 might be involved in the pathologic progression of HCC.
背景
免疫抑制受体 LILRB1 通过细胞内免疫受体酪氨酸抑制基序传递免疫抑制信号，调节肿瘤进展。然而，其在肝细胞癌（HCC）中的作用尚不清楚。
目的
本研究旨在揭示 LILRB1 与 HCC 之间的关联。
方法
采用免疫印迹和 qRT-PCR 检测肝癌细胞中 LILRB1 的水平。采用免疫组织化学染色检测组织芯片中 LILRB1 阳性细胞。利用基因表达谱交互分析（GEPIA）和 Oncomine 数据库分析 LILRB1、SHP1 和 SHP2 之间的关系及其与生存率的关系。
结果
与正常细胞相比，肝癌细胞中 LILRB1 水平明显降低。临床上，75 对配对癌旁组织中有 49 对（65%）的 LILRB1 水平高于配对 HCC 样本，75 例 HCC 患者中有 48 例（64%）的 LILRB1 水平较低，而在配对的癌旁组织中有 25 例（33%）。Oncomine 数据库和 GEPIA 分析证实，LILRB1 在 HCC 中的表达低于正常组织。此外，低 LILRB1 与 HCC 患者的临床病理特征和无病生存率显著相关，但与总生存率无关。机制上，在 HCC 中观察到 LILRB1 与 SHP1 呈正相关，而与 SHP2 无关。
结论
LILRB1 可能通过整合 SHP1 在肝癌细胞中发挥抗肿瘤作用，为 LILRB1 可能参与 HCC 病理进展提供了证据。
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