A Pan-Cancer Analysis Reveals CLEC5A as a Biomarker for Cancer Immunity and Prognosis

Rui Chen; Wantao Wu; Si-Yu Chen; Zheng-Zheng Liu; Zhi-Peng Wen; Jing Yu; Long-Bo Zhang; Zaoqu Liu; Jian Zhang; Peng Luo; Wen-Jing Zeng; Quan Cheng

doi:10.3389/fimmu.2022.831542

A Pan-Cancer Analysis Reveals CLEC5A as a Biomarker for Cancer Immunity and Prognosis

Front Immunol. 2022 Aug 1:13:831542. doi: 10.3389/fimmu.2022.831542. eCollection 2022.

Authors

Rui Chen¹, Wantao Wu^{2

3

4}, Si-Yu Chen^{2

4

5}, Zheng-Zheng Liu^{3

4}, Zhi-Peng Wen⁵, Jing Yu^{4

6}, Long-Bo Zhang^{4

7}, Zaoqu Liu⁸, Jian Zhang⁹, Peng Luo⁹, Wen-Jing Zeng^{4

5}, Quan Cheng^{2

4}

Affiliations

¹ Department of Neurosurgery, The Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Hengyang, China.
² Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
³ Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.
⁴ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
⁵ Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China.
⁶ Department of Pharmacy, The Affiliated Hospital of Guizhou Medical University, Guizhou Medical University, Guiyang, China.
⁷ Department of Neurosurgery, and Department of Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, CT, United States.
⁸ Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
⁹ Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Abstract

Background: CLEC5A is a member of the C-type lectin superfamily. It can activate macrophages and lead to a series of immune-inflammation reactions. Previous studies reveal the role of CLEC5A in infection and inflammation diseases.

Method: We acquire and analyze data from The Cancer Genome Atlas (TCGA) database, Genotype-Tissue Expression (GTEx) database, and other comprehensive databases via GSCALite, cBioPortal, and TIMER 2.0 platforms or software. Single-cell sequencing analysis was performed for quantifying the tumor microenvironment of several types of cancers.

Results: CLEC5A is differentially expressed in a few cancer types, of which overexpression accompanies low overall survival of patients. DNA methylation mainly negatively correlates with CLEC5A expression. Moreover, CLEC5A is positively related to immune infiltration, including macrophages, cancer-associated fibroblasts (CAFs), and regulatory T cells (Tregs). Immune checkpoint genes are significantly associated with CLEC5A expression in diverse cancers. In addition, CLEC5A expression correlates with mismatch repair (MMR) in several cancers. Tumor mutation burden (TMB), microsatellite instability (MSI), and neoantigens show a positive association with CLEC5A expression in several cancers. Furthermore, CLEC5A in cancer correlates with signal transduction, the immune system, EMT, and apoptosis process. The drug sensitivity analysis screens out potential therapeutic agents associated with CLEC5A expression, including FR-180204, Tivozanib, OSI-930, Linifanib, AC220, VNLG/124, Bexarotene, omacetaxine mepesuccinate, narciclasine, leptomycin B, PHA-793887, LRRK2-IN-1, and CR-1-31B.

Conclusion: CLEC5A overexpresses in multiple cancers in contrast to normal tissues, and high CLEC5A expression predicts poor prognosis of patients and immune infiltration. CLEC5A is a potential prognostic biomarker of diverse cancers and a target for anti-tumor therapy.

Keywords: CLEC5A; cancer immune; immunotherapy; pan-cancer; prognostic biomarkers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers, Tumor / genetics
Humans
Inflammation
Lectins, C-Type / genetics
Neoplasms* / genetics
Prognosis
Receptors, Cell Surface* / metabolism
Tumor Microenvironment / genetics

Substances

Biomarkers, Tumor
CLEC5A protein, human
Lectins, C-Type
Receptors, Cell Surface