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趋化因子受体 2 在卵巢癌中的预后和免疫意义：用于生存结局和免疫治疗反应评估的有前途的靶点。

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

机构信息

Department of Gynecologic Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, 350014 Fujian, China.

Department of Oncological Nursing, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, 350014 Fujian, China.

出版信息

Dis Markers. 2021 Nov 19;2021:5350232. doi: 10.1155/2021/5350232. eCollection 2021.

DOI:10.1155/2021/5350232
PMID:34840630
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8626184/
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.

摘要

目的

揭示肿瘤的遗传和免疫特征对于深入了解免疫治疗反应的机制至关重要。本研究观察了 CXCR2 在卵巢癌中的预后和免疫学功能。

方法

基于 TCGA 和 GTEx 数据集，分析了 CXCR2 在多种癌症类型中的表达、预后意义和基因突变。评估了 CXCR2 表达与免疫检查点、新抗原、肿瘤突变负担（TMB）和微卫星不稳定性（MSI）在泛癌症中的相关性。鉴定了与 CXCR2 相关的基因，并在卵巢癌中研究了它们的生物学功能。通过三种算法（TIMER、quanTIseq 和 xCell），我们评估了 CXCR2 与卵巢癌中免疫细胞浸润的关系。采用 GSEA 推断 CXCR2 相关的 KEGG 和标志性途径。

结果

CXCR2 在泛癌症中肿瘤组织中的表达异常，高于配对的正常组织。在卵巢癌中，CXCR2 的表达更高。此外，它的表达与总生存期和进展有关，包括卵巢癌。在人类癌症中，CXCR2 与免疫检查点、新抗原、TMB 和 MSI 有显著关联。CXCR2 在泛癌症中经常发生体细胞突变。在卵巢癌中，扩增是 CXCR2 的主要突变类型。CXCR2 相关基因在卵巢癌中明显富集于免疫激活和致癌途径。此外，它参与调节卵巢癌肿瘤微环境中的免疫细胞浸润，如巨噬细胞，并且免疫反应明显受到 CXCR2 的调节。

结论

总之，CXCR2 作为一种有前途的预后和免疫生物标志物以及卵巢癌的新型免疫治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e2a/8626184/7b74cf186b1d/DM2021-5350232.007.jpg
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