ACE2 correlated with immune infiltration serves as a prognostic biomarker in endometrial carcinoma and renal papillary cell carcinoma: implication for COVID-19

ACE2 correlated with immune infiltration serves as a prognostic biomarker in endometrial carcinoma and renal papillary cell carcinoma: implication for COVID-19
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与免疫浸润相关的 ACE2 作为子宫内膜癌和肾乳头状细胞癌的预后生物标志物:对 COVID-19 的影响

DOI:
10.18632/aging.103100
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发表时间:
2020-04-30
期刊:
影响因子:
5.2
通讯作者:
Zhou, Yafeng
Zhou, Yafeng
中科院分区:
医学2区
文献类型:
--
作者:
Yang, Jing;Li, Hongxia;Zhou, Yafeng

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血管紧张素转换酶2(ACE 2)是肾素-血管紧张素系统的一员,但ACE 2与子宫体子宫内膜癌(UCEC)和肾乳头状细胞癌(KIRP)预后的关系尚不清楚。我们分析了Oncomine和TIMER数据库中ACE 2的表达水平,以及PrognoScan、GEPIA和Kaplan-Meier SPSS数据库中ACE 2与总生存期的相关性。在TIMER数据库中分析ACE 2与免疫浸润水平及免疫细胞类型标志物的相关性。进一步对相关免疫细胞亚群中ACE 2的表达水平进行预后分析。在UALCAN数据库中测试ACE 2启动子甲基化谱。此外,我们使用GSE 30589和GSE 52920数据库来阐明SARS-CoV感染后体内和体外ACE 2表达的变化。ACE 2在UCEC和KIRP中升高,高ACE 2预后良好。UCEC中ACE 2的表达与KIRP中巨噬细胞的免疫浸润水平、B细胞、CD 4 +T细胞、中性粒细胞和树突状细胞的免疫浸润水平呈正相关。UCEC中ACE 2与B细胞、中性粒细胞、巨噬细胞的类型标志物呈显著正相关,KIRP中ACE 2与巨噬细胞的类型标志物呈显著正相关。UCEC和KIRP中ACE 2高表达的不同免疫细胞亚群预后良好。UCEC和KIRP中ACE 2基因启动子甲基化水平显著降低。此外,我们还发现SARS-CoV感染后,ACE 2在体内和体外的表达均下降。结论:ACE 2在UCEC和KIRP中表达明显增高,ACE 2表达增高与免疫浸润和预后呈正相关。此外,在患有UCEC和KIRP的COVID-19患者中,肿瘤组织可能更容易感染SARS-CoV-2,这可能会恶化预后。
Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotension system, however, the correlation between ACE2 and prognosis in UCEC (Uterine Corpus Endometrial Carcinoma) and KIRP (Kidney Renal Papillary Cell Carcinoma) is not clear. We analyzed the expression levels of ACE2 in the Oncomine and TIMER databases, the correlation between ACE2 and overall survival in the PrognoScan, GEPIA and Kaplan-Meier plotter databases. The correlation between ACE2 and immune infiltration level and the type markers of immune cells was investigated in TIMER database. A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. The ACE2 promoter methylation profile was tested in the UALCAN database. In addition, we used GSE30589 and GSE52920 databases to elucidate the changes of ACE2 expression in vivo and in vitro after SARS-CoV infection. ACE2 was elevated in UCEC and KIRP, and high ACE2 had a favorable prognosis. The expression of ACE2 was positively correlated with the level of immune infiltration of macrophage in KIRP, B cell, CD4+T cell, neutrophil and dendritic cell immune infiltration levels in UCEC. ACE2 was significantly positively correlated with the type markers of B cells and neutrophils, macrophages in UCEC, while ACE2 in KIRP was positively correlated with the type markers of macrophages. High ACE2 expression level had a favorable prognosis in different enriched immune cells subgroups in UCEC and KIRP. And the promoter methylation levels of ACE2 in UCEC and KIRP were significantly reduced. What’s more, we found that the expression of ACE2 decreased in vivo and in vitro after SARS-CoV infection. In conclusion, ACE2 expression increased significantly in UCEC and KIRP, elevated ACE2 was positively correlated with immune infiltration and prognosis. Moreover, tumor tissues may be more susceptible to SARS-CoV-2 infection in COVID-19 patients with UCEC and KIRP, which may worsen the prognosis.