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

Fu Wang,Haizhou Ji,Tongyu Liu,Mi Ren,Yang Sun

doi:10.1155/2021/5350232

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.

Highlights

Ovarian cancer represents the major cause of deaths of gynecological malignancies [1, 2]
Upregulation of CXCR2 expression was found in KIRC, LAML, LGG, OV, PAAD, STAD, and TGCT
Using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) tool, the relationships of CXCR2 expression with pathological staging were evaluated in CHOL, COAD, ESCA, KIRC, OV, PAAD, READ, and STAD (Figure 1(c))

Summary

Introduction

Ovarian cancer represents the major cause of deaths of gynecological malignancies [1, 2]. Epithelial ovarian cancer is the most common form [3]. The present first-line standards of care include debulking surgery plus platinum–taxane maintenance chemotherapeutic strategy [5]. The high mortality of ovarian cancer patients can be attributed to chemotherapy resistance, extensive intraperitoneal metastasis, and other factors [7]. Awful mortality may be attributed chemotherapeutic resistance, extensive intraperitoneal metastases, etc. Tumor microenvironment exerts a critical role in the progression and clinical outcomes of ovarian cancer [9]. Emerging immunotherapeutic strategies enhance the antitumor immune response by diverse methods such as immunostimulatory cytokine and tumor antigen vaccine as well as monoclonal antibody [10].

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Results

Discussion

Conclusion