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卵巢癌微环境中 CXC 趋化因子的筛选及 CXCL10 的生物学功能。

Screening of CXC chemokines in the microenvironment of ovarian cancer and the biological function of CXCL10.

机构信息

School of Medicine, Yunnan University, No.2, Cuihu North Road, Kunming, 650091, Yunnan Province, People's Republic of China.

出版信息

World J Surg Oncol. 2021 Nov 18;19(1):329. doi: 10.1186/s12957-021-02440-x.

Abstract

BACKGROUND

This study aims to screen and identify the biological functions and prognostic value of CXC chemokines in ovarian cancer (OC) through bioinformatics and molecular biology methods, and to provide data support for the selection of biomarkers and prognostic analysis of OC.

METHODS

In this study, GEO, ONCOMINE, GEPIA, cBioPortal, GeneMANIA, Metascape, STRING, TRRUST, and TIMER databases were used to study CXC chemokines. Angiogenesis and T cell killing assay were used to detect the effect of CXCL10 on tumor cell immunity and angiogenesis. Real-time quantitative PCR (qRT-PCR), immunoblotting, and ectopic tumor formation experiments were used to verify the effect of CXCL10 on ovarian cancer tumors.

RESULTS

We found that CXCL1, CXCL10, CXCL11, CXCL13, and CXCL14 were significantly upregulated in OC samples compared with normal tissues. Our data showed that there was a relationship between the expression of CXC chemokines and the infiltration of six types of immune cells significant correlation. In vitro assay confirmed that overexpression of CXCL10 could enhance the killing effect of T cells and inhibit angiogenesis. Further in vivo assay had shown that CXCL10 could affect the progression of ovarian cancer by increasing the expression of cytotoxic T cells and inhibiting angiogenesis.

CONCLUSION

In conclusion, we hope that our data will provide new insights into the development of immunotherapy and the selection of prognostic markers for patients with OC.

摘要

背景

本研究旨在通过生物信息学和分子生物学方法筛选和鉴定卵巢癌(OC)中 CXC 趋化因子的生物学功能和预后价值,并为 OC 生物标志物的选择和预后分析提供数据支持。

方法

本研究使用 GEO、ONCOMINE、GEPIA、cBioPortal、GeneMANIA、Metascape、STRING、TRRUST 和 TIMER 数据库研究 CXC 趋化因子。通过血管生成和 T 细胞杀伤试验检测 CXCL10 对肿瘤细胞免疫和血管生成的影响。实时定量 PCR(qRT-PCR)、免疫印迹和异位肿瘤形成实验用于验证 CXCL10 对卵巢癌细胞的影响。

结果

我们发现与正常组织相比,OC 样本中 CXCL1、CXCL10、CXCL11、CXCL13 和 CXCL14 的表达显著上调。我们的数据表明 CXC 趋化因子的表达与六种免疫细胞浸润之间存在显著相关性。体外试验证实 CXCL10 的过表达可增强 T 细胞的杀伤作用并抑制血管生成。进一步的体内试验表明,CXCL10 通过增加细胞毒性 T 细胞的表达和抑制血管生成来影响卵巢癌的进展。

结论

总之,我们希望我们的数据将为 OC 患者的免疫治疗发展和预后标志物的选择提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a4a/8600898/d031c7df5d20/12957_2021_2440_Fig1_HTML.jpg

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