Jing Qiangan, Yuan Chen, Zhou Chaoting, Jin Weidong, Wang Aiwei, Wu Yanfang, Shang Wenzhong, Zhang Guibing, Ke Xia, Du Jing, Li Yanchun, Shao Fangchun
Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Department of Central Laboratory, Affiliated Hangzhou first people's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Cancer Cell Int. 2023 Jun 12;23(1):113. doi: 10.1186/s12935-023-02939-1.
C-type lectin domain family 1 member B (CLEC1B, encoding the CLEC-2 protein), a member of the C-type lectin superfamily, is a type II transmembrane receptor involved in platelet activation, angiogenesis, and immune and inflammatory responses. However, data regarding its function and clinical prognostic value in hepatocellular carcinoma (HCC) remain scarce.
The expression of CLEC1B was explored using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RT-qPCR, western blot, and immunohistochemistry assays were employed to validate the downregulation of CLEC1B. Univariate Cox regression and survival analyses were used to evaluate the prognostic value of CLEC1B. Gene Set Enrichment Analysis (GSEA) was conducted to investigate the potential association between cancer hallmarks and CLEC1B expression. The TISIDB database was applied to search for the correlation between immune cell infiltration levels and CLEC1B expression. The association between CLEC1B and immunomodulators was conducted by Spearman correlation analysis based on the Sangerbox platform. Annexin V-FITC/PI apoptosis kit was used for the detection of cell apoptosis.
The expression of CLEC1B was low in various tumors and exhibited a promising clinical prognostic value for HCC patients. The expression level of CLEC1B was tightly associated with the infiltration of various immune cells in the HCC tumor microenvironment (TME) and positively correlated with a bulk of immunomodulators. In addition, CLEC1B and its related genes or interacting proteins are implicated in multiple immune-related processes and signaling pathways. Moreover, overexpression of CLEC1B significantly influenced the treatment effects of sorafenib on HCC cells.
Our results reveal that CLEC1B could serve as a potential prognostic biomarker and may be a novel immunoregulator for HCC. However, its function in immune regulation should be further explored.
C型凝集素结构域家族1成员B（CLEC1B，编码CLEC-2蛋白）是C型凝集素超家族的成员，是一种II型跨膜受体，参与血小板活化、血管生成以及免疫和炎症反应。然而，关于其在肝细胞癌（HCC）中的功能和临床预后价值的数据仍然匮乏。
利用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）探索CLEC1B的表达。采用逆转录定量聚合酶链反应（RT-qPCR）、蛋白质免疫印迹和免疫组织化学分析来验证CLEC1B的下调。采用单因素Cox回归和生存分析来评估CLEC1B的预后价值。进行基因集富集分析（GSEA）以研究癌症特征与CLEC1B表达之间的潜在关联。应用TISIDB数据库搜索免疫细胞浸润水平与CLEC1B表达之间的相关性。基于Sangerbox平台，通过Spearman相关性分析研究CLEC1B与免疫调节剂之间的关联。使用膜联蛋白V-异硫氰酸荧光素/碘化丙啶（Annexin V-FITC/PI）凋亡试剂盒检测细胞凋亡。
CLEC1B在多种肿瘤中表达较低，对HCC患者具有良好的临床预后价值。CLEC1B的表达水平与HCC肿瘤微环境（TME）中多种免疫细胞的浸润密切相关，并且与大量免疫调节剂呈正相关。此外，CLEC1B及其相关基因或相互作用蛋白参与多个免疫相关过程和信号通路。此外，CLEC1B的过表达显著影响索拉非尼对HCC细胞的治疗效果。
我们的结果表明，CLEC1B可作为潜在的预后生物标志物，可能是HCC的新型免疫调节剂。然而，其在免疫调节中的功能有待进一步探索。
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