An Integrated Analysis of C5AR2 Related to Malignant Properties and Immune Infiltration of Breast Cancer.

An Integrated Analysis of C5AR2 Related to Malignant Properties and Immune Infiltration of Breast Cancer.
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C5AR2与乳腺癌恶性特性及免疫浸润相关的综合分析

DOI:
10.3389/fonc.2021.736725
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发表时间:
2021
影响因子:
4.7
通讯作者:
Hu W
Hu W
中科院分区:
医学3区
文献类型:
--
作者:
Zhu Y;Wang X;Xu Y;Chen L;Ding P;Chen J;Hu W

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背景C5AR 2(GPR77,C5L2)是C5a的第二种受体,C5a是由补体激活产生的有效蛋白。C5AR 2可以介导其自身的信号传导事件,并通过这些事件发挥显著的免疫调节作用。然而,C5AR 2在癌症中的研究有限,其在乳腺癌中的功能仍不清楚。方法应用GTEx、TCGA、PrognoScan、TIMER 2. 0、CCLE、HPA、TISIDB等数据库,分析30余种肿瘤组织中C5AR 2的表达及其与预后、免疫浸润、肿瘤突变负荷(TMB)、微卫星不稳定性(MSI)的关系。C5AR 2与乳腺癌中的那些免疫标记物组显示出强相关性。另外,通过CCK 8法和Transwell法分析C5AR 2在乳腺癌细胞迁移、侵袭和增殖中的作用。结果C5AR 2在大多数癌组织和非癌组织中的表达存在差异,在BRCA、GBM、KICH、LAML、LGG、LIHC、PAAD和STAD中,C5AR 2高表达与预后不良显著相关。此外,C5AR 2表达水平与公认的免疫浸润显著相关,特别是乳腺癌中巨噬细胞的极化。基因集富集分析证实C5AR 2参与调节肿瘤发生以及肿瘤免疫中涉及的多个信号通路。C5AR 2过表达促进了乳腺癌细胞的迁移、侵袭和增殖等功能,这与生物信息学分析一致。结论C5AR 2参与了乳腺癌的免疫浸润和恶性特征,可能成为乳腺癌的一个有前景的生物标志物。
Background C5AR2 (GPR77, C5L2) is the second receptor for C5a that is a potent protein generated by complement activation. C5AR2 can mediate its own signaling events and exert significant immunomodulatory effects through those events. However, research of C5AR2 in cancer is limited, and its function remains unclear in breast cancer. Methods The expression of C5AR2 and its correlations with prognosis, immune infiltration, tumor mutation burden (TMB), and microsatellite instability (MSI) in more than thirty types of cancers were described through GTEx, TCGA, PrognoScan, TIMER2.0, CCLE, HPA, and TISIDB database. C5AR2 showed strong relationships to those immune marker sets in breast cancer. Otherwise, CCK8 assay and Transwell assay were conducted to illustrate the role of C5AR2 in migration, invasion, and proliferation of breast cancer cells. Results Generally, C5AR2 expression differed across most cancerous and noncancerous tissues, and high C5AR2 expression significantly related to poor prognosis in BRCA, GBM, KICH, LAML, LGG, LIHC, PAAD, and STAD. Moreover, C5AR2 expression levels were dramatically correlated with recognized immune infiltration, especially the polarization of macrophages in breast cancer. Gene set enrichment analysis confirmed that C5AR2 participates in regulating multiple signaling pathways involved in tumorigenesis as well as tumor immunity. C5AR2 overexpression facilitated the functions such as migration, invasion, and proliferation in breast cancer cells, which is consistent with bioinformatics analysis. Conclusions C5AR2 is involved in immune infiltration and malignant characteristics of breast cancer, which may be a prospective biomarker for breast cancer.
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