Department of Clinical Laboratory, Taizhou First People's Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, China.
Department of Clinical Laboratory, Taizhou Hospital of Zhengjiang Province affiliated of Wenzhou Medical University, Linhai, China.
J Clin Lab Anal. 2022 Jun;36(6):e24362. doi: 10.1002/jcla.24362. Epub 2022 Apr 4.
Breast cancer is a frequently occurring malignant tumor in women. Angiotensin-converting enzyme 2 (ACE2) is widely expressed in most organs; however, the association of ACE2 with prognosis and immune infiltration in breast invasive carcinoma (BRCA) remains elusive.
We explored the expression level and prognostic value of ACE2 in patients with BRCA using a series of online bioinformatics analysis databases encompassing Oncomine, UALCAN, Kaplan-Meier plotter, TIMER, LinkedOmics, and GEO. qRT-PCR was performed to verify our findings.
Angiotensin-converting enzyme 2 mRNA and protein expression levels were decreased in BRCA tissues, and patients with low ACE2 expression levels had a poor prognosis. DNA promoter methylation of ACE2 significantly downregulated ACE2 expression in BRCA, while the expression of this protein was positively linked to immune infiltration of B cells, CD8 and CD4 T cells, neutrophils, and dendritic cells in BRCA tissues. The high expression level of ACE2 in enriched basophils, CD8 T cells, and type-2 helper T cells, which showed decreasing levels, indicated a better prognosis for BRCA. Enrichment analyses revealed that NF-κB, IL-17, and TNF signaling pathways were highly correlated to ACE2 in BRCA. Verification study revealed that downregulation of ACE2 was associated with a better prognosis in BRCA. Univariate and multivariate analysis confirmed ACE2 expression and clinical stage as independent prognostic factors for breast cancer.
Angiotensin-converting enzyme 2 may be a potential prognostic biomarker and target for BRCA. Nevertheless, future investigations are needed for validating our findings and promoting the clinical application of ACE2 in BRCA.
乳腺癌是女性中常见的恶性肿瘤。血管紧张素转换酶 2（ACE2）广泛表达于大多数器官；然而，ACE2 与乳腺浸润性癌（BRCA）的预后和免疫浸润的关系仍不清楚。
我们使用 Oncomine、UALCAN、Kaplan-Meier plotter、TIMER、LinkedOmics 和 GEO 等一系列在线生物信息学分析数据库，探讨了 ACE2 在 BRCA 患者中的表达水平和预后价值。通过 qRT-PCR 验证了我们的发现。
ACE2 mRNA 和蛋白表达水平在 BRCA 组织中降低，ACE2 低表达的患者预后不良。BRCA 中 ACE2 的 DNA 启动子甲基化显著下调 ACE2 的表达，而该蛋白的表达与 BRCA 组织中 B 细胞、CD8 和 CD4 T 细胞、中性粒细胞和树突状细胞的免疫浸润呈正相关。BRCA 中富集的嗜碱性粒细胞、CD8 T 细胞和 2 型辅助 T 细胞中 ACE2 表达水平较高，表明预后较好。富集分析表明，NF-κB、IL-17 和 TNF 信号通路与 BRCA 中的 ACE2 高度相关。验证研究表明，ACE2 的下调与 BRCA 的良好预后相关。单因素和多因素分析证实 ACE2 表达和临床分期是乳腺癌的独立预后因素。
血管紧张素转换酶 2（ACE2）可能是 BRCA 的一个潜在预后生物标志物和治疗靶点。然而，需要进一步的研究来验证我们的发现，并促进 ACE2 在 BRCA 中的临床应用。
