Pan-Cancer Analysis Identified CD93 as a Valuable Biomarker for Predicting Patient Prognosis and Immunotherapy Response.

Tao Cui,Guangyu Wang,Zirong Liu,Liuyang Zhu,Yamin Zhang,Long Yang,Yi Bai,Hao Wu,Wen Tong

doi:10.3389/fmolb.2021.793445

Abstract

Background: The rapid development of immunotherapy has significantly improved patient outcomes in recent years. CD93, a novel biomarker expressed on vascular endothelial cells, is essential for tumor angiogenesis. Recent studies have shown that CD93 is closely related to immune cell infiltration and immunotherapy. However, its role in pan-cancer has not been reported. Methods: The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), cbioportal, Gene Expression Omnibus (GEO), Tumor Immune Estimation Resource (TIMER2.0), and the Tumor–Immune System Interactions and Drug Bank (TISIDB) databases were used to analyze CD93 in pan-cancers. R software was used for statistical analysis and mapping. Results: There were significant differences in the expression of CD93 between tumor tissues and adjacent normal tissues in pan-cancer. The high expression of CD93 was associated with poor prognosis and high TNM stage in multiple tumor types. However, a high expression of CD93 was a protective factor in kidney renal clear cell carcinoma (KIRC). In addition, CD93 was closely related to immune cell infiltration in tumor tissues. Moreover, CD93 presented a robust correlation with immune modulators and immunotherapeutic markers [e.g., tumor mutation burden (TMB) and microsatellite instability (MSI)]. The results of gene set enrichment analysis (GSEA) showed that CD93 was correlated with tumor angiogenesis. Importantly, patients with a low expression of CD93 were more sensitive to immunotherapy in urothelial cancer. Conclusion: CD93, which is involved in various immune responses, controls immune cell infiltration and impacts on the malignant properties of various cancer types. Therefore, CD93 has potential value to be biomarker for determining the prognosis and immune infiltration in multiple cancers.

Highlights

The latest research revealed that tumor angiogenesis involved a series of complex processes, including the regulation of endothelial cell migration and extracellular matrix deposition (Liao et al, 2020; Mao et al, 2020; Unterleuthner et al, 2020)
A high expression of CD93 was a protective factor in kidney renal clear cell carcinoma (KIRC)
CD93 presented a robust correlation with immune modulators and immunotherapeutic markers [e.g., tumor mutation burden (TMB) and microsatellite instability (MSI)]

Summary

Introduction

The latest research revealed that tumor angiogenesis involved a series of complex processes, including the regulation of endothelial cell migration and extracellular matrix deposition (Liao et al, 2020; Mao et al, 2020; Unterleuthner et al, 2020). Endothelial cell migration is essential to angiogenesis, enabling the outgrowth of new blood vessels both in physiological and pathological contexts. Growing evidence indicated that CD93 plays an important regulatory role in tumor angiogenesis (Lugano et al, 2018; Barbera et al, 2021). The interaction of CD93 and MMRN2 can promote endothelial cell adhesion and migration, promoting pathological angiogenesis (Galvagni et al, 2017). CD93 could promote β1 integrin activation and fibronectin fibrillogenesis, performing a significant role in vascular maturation and formation of the extracellular matrix during tumor angiogenesis (Lugano et al, 2018). Studies have shown that CD93 controls the migration of endothelial cells by activating the small GTPase of Rho family (Barbera et al, 2019). Its role in pan-cancer has not been reported

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Discussion

Conclusion