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ACE2对乳腺癌预后的影响及其潜在机制

Effect of ACE2 on the prognosis of breast cancer and its potential mechanism

  • 摘要: 研究跨膜蛋白血管紧张素转换酶2(angiotensin converting enzyme 2,ACE2)对乳腺癌预后的影响及其潜在机制。使用公共数据库分析ACE2表达和与乳腺癌患者临床病理特征、患者预后及免疫微环境的关系;结合体外实验分析ACE2在乳腺癌中的作用机制。研究结果显示,ACE2在乳腺癌组织中的表达明显低于乳腺正常组织,其表达与乳腺癌患者的年龄、M分期和N1mi期显著负相关(P < 0.05)。ACE2高表达的Luminal型乳腺癌患者预后不良,而在三阴性乳腺癌(triple-negative breast cancer,TNBC)亚型中,ACE2则展现出不同的预后意义。此外,ACE2还与肿瘤组织的代谢和免疫微环境密切相关。体外实验表明,ACE2在MDA-MB-231细胞中低表达,并可能通过下调基质金属蛋白酶2(MMP2)来抑制细胞的进展。研究结果提示,ACE2在乳腺癌中低表达,与患者的预后及代谢和免疫微环境密切相关,其可能是通过MMP2途径抑制TNBC细胞进展。

     

    Abstract: This study aims to investigate the effect of transmembrane protein angiotensin converting enzyme 2 (ACE2) on the prognosis of breast cancer and its potential mechanism.Public databases were used to analyze ACE2 expression and its relationship with clinicopathological features and prognosis of breast cancer patients, combined with in vitro experiments to analyze the mechanism of action and immune relevance of ACE2 in breast cancer.Results showed that the expression of ACE2 in breast cancer tissues was significantly lower than that in normal breast tissues, and that its expression was negatively correlated with age, M stage and N1mi stage of breast cancer patients (P < 0.05).Patients with Luminal type breast cancer with high ACE2 expression had poor prognosis, while in the triple-negative breast cancer (TNBC) subtype, ACE2 showed different prognostic significance.In addition, ACE2 is closely associated with the metabolic and immune microenvironment of tumor tissue.In vitro experiments have shown that ACE2 is lowly expressed in MDA-MB-231 cells and may inhibit cell progress by downregulating matrix metalloproteinase 2(MMP2).The results suggest that the low expression of ACE2 in breast cancer is closely associated with patient prognosis as well as metabolic and immune microenvironment, and that ACE2 may inhibit TNBC cell progress through the MMP2 pathway.

     

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