Prognostic and Immunological Significance of CXCR2 in Ovarian Cancer: A Promising Target for Survival Outcome and Immunotherapeutic Response Assessment.

Abstract

OBJECTIVE:

Uncovering genetic and immunologic tumor features is critical to gain insights into the mechanisms of immunotherapeutic response. Herein, this study observed the functions of CXCR2 in prognosis and immunology of ovarian cancer.

METHODS:

Expression, prognostic significance, and genetic mutations of CXCR2 were analyzed in diverse cancer types based on TCGA and GTEx datasets. Associations of CXCR2 expression with immune checkpoints, neoantigens, tumor mutational burden (TMB), and microsatellite instability (MSI) were evaluated across pancancer. CXCR2-relevant genes were identified, and their biological functions were investigated in ovarian cancer. Through three algorithms (TIMER, quanTIseq, and xCell), we assessed the relationships of CXCR2 with immune cell infiltration in ovarian cancer. GSEA was adopted for inferring KEGG and hallmark pathways involved in CXCR2.

RESULTS:

CXCR2 presented abnormal expression in tumors than paired normal tissues across pancancer. Higher expression of CXCR2 was found in ovarian cancer. Moreover, its expression was in relation to overall survival and progression including ovarian cancer. Prominent associations of CXCR2 with immune checkpoints, neoantigens, TMB, and MSI were observed in human cancers. Somatic mutations of CXCR2 frequently occurred across pancancer. Amplification was the main mutational type of CXCR2 in ovarian cancer. CXCR2-relevant genes were markedly enriched in immunity activation and carcinogenic pathways in ovarian cancer. Moreover, it participated in modulating immune cell infiltration in the tumor microenvironment of ovarian cancer such as macrophage and immune response was prominently modulated by CXCR2.

CONCLUSION:

Collectively, CXCR2 acts as a promising prognostic and immunological biomarker as well as a novel immunotherapeutic target of ovarian cancer.

• Authors: Haizhou Ji, Mi Ren, Tongyu Liu, Yang Sun
• Journal: Disease markers (Dis Markers) Vol. 2021 Pg. 5350232 ( 2021) ISSN: 1875-8630 [Electronic] United States
• PMID: 34840630 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Haizhou Ji et al.

Chemical References

• Biomarkers, Tumor
• CXCR2 protein, human
• Immune Checkpoint Inhibitors
• Receptors, Interleukin-8B

Topics

• Biomarkers, Tumor (genetics)
• Case-Control Studies
• Female
• Follow-Up Studies
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Immune Checkpoint Inhibitors (therapeutic use)
• Microsatellite Instability
• Mutation
• Ovarian Neoplasms (drug therapy, genetics, immunology, mortality)
• Prognosis
• Receptors, Interleukin-8B (genetics)
• Survival Rate
• Tumor Microenvironment