Comprehensive analysis identifies CLEC1B as a potential prognostic biomarker in hepatocellular carcinoma

Qiangan Jing; Chen Yuan; Chaoting Zhou; Weidong Jin; Aiwei Wang; Yanfang Wu; Wenzhong Shang; Guibing Zhang; Xia Ke; Jing Du; Yanchun Li; Fangchun Shao

doi:10.1186/s12935-023-02939-1

Comprehensive analysis identifies CLEC1B as a potential prognostic biomarker in hepatocellular carcinoma

Cancer Cell Int. 2023 Jun 12;23(1):113. doi: 10.1186/s12935-023-02939-1.

Authors

Qiangan Jing^#^{1

2

3}, Chen Yuan^#¹, Chaoting Zhou^#^{1

3}, Weidong Jin¹, Aiwei Wang⁴, Yanfang Wu⁴, Wenzhong Shang⁴, Guibing Zhang⁴, Xia Ke³, Jing Du⁵, Yanchun Li⁶, Fangchun Shao⁷

Affiliations

¹ Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
² Department of Central Laboratory, Affiliated Hangzhou first people's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
³ College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, Zhejiang, China.
⁴ Department of Hematology, The first people's Hospital of Fuyang Hangzhou, Hangzhou, Zhejiang, China.
⁵ Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. dujing1@hmc.edu.cn.
⁶ Department of Central Laboratory, Affiliated Hangzhou first people's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China. lycmed@163.com.
⁷ Cancer Center, Department of Pulmonary and Critical Care Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China. shaofc@139.com.

^# Contributed equally.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Biomarker; CLEC1B; Hepatocellular carcinoma; Immunoregulator; Sorafenib; Tumor microenvironment.

Abstract

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