基于生物信息学分析MMP11基因在乳腺癌中的表达及临床意义

Bioinformatics Analysis of MMP11 Expression and Clinical Significance in Breast Cancer

摘要: 目的：使用多种生信数据库在线分析基质金属蛋白酶-11 (MMP11)基因在乳腺癌中的表达差异及临床意义，探索治疗乳腺癌的新靶点。方法：应用多种在线生物信息学数据库分析乳腺癌细胞及组织中MMP11的表达水平与临床病理和肿瘤干细胞的关系；应用UALCAN数据库分析MMP11基因与甲基化之间的关系；应用KM Plotter数据库分析MMP11的表达与乳腺癌临床特征和预后的关系；应用Cancer SEA数据库分析MMP11在单个细胞中的功能相关性。结果：MMP11在乳腺癌患者中(n = 1085)高表达，在Luminal 型、1期以及淋巴结N3的患者中尤为显著(P < 0.05)；在乳腺癌微环境中，MMP11的表达与干细胞标志物CD133、Oct4的水平均呈负相关(P < 0.05)，与干细胞标志物ANTXR1、CD55水平呈正相关(P < 0.05)；MMP11是一种去甲基化基因，且在正常乳腺组织与乳腺癌组织中差异表达(P < 0.05)；MMP11的表达量越高的乳腺癌患者的总生存期越短，在Luminal A、Luminal B、Her-2过表达型及淋巴结阴性的乳腺癌患者中有统计学意义(P < 0.05)；在单细胞水平，MMP11基因的表达与表皮间质转化、增殖效应呈显著负相关(r = −0.60、−0.54，P均<0.05)。结论：在乳腺癌患者中MMP11高表达，且表达水平与患者的生存预后相关，推测MMP11是乳腺癌诊断和治疗的一个潜在靶点。

Abstract: Objective: To analyze the expression differences and clinical significance of matrix metalloproteinase-11 (MMP11) gene in breast cancer using a variety of bioinformatics databases, and to explore new targets for the treatment of breast cancer. Methods: A variety of online bioinformatics databases were used to analyze the relationship between MMP11 expression levels and clinicopathological and cancer stem cells in breast cancer cells and tissues. The UALCAN database was used to analyze the relationship between MMP11 gene and methylation. KM Plotter database was used to analyze the relationship between MMP11 expressions and clinical features and prognosis of breast cancer. The Cancer SEA database was used to analyze the functional correlation of MMP11 in a single cell. Results: MMP11 was highly expressed in breast cancer patients (n = 1085), especially in patients with luminal type, stage 1 and lymph node N3 (P < 0.05). In the breast cancer microenvironment, the expression of MMP11 was negatively correlated with the levels of stem cell markers CD133 and Oct4 (P < 0.05), and positively correlated with the levels of stem cell markers ANTXR1 and CD55 (P < 0.05). MMP11 is a demethylating gene and is differentially expressed in normal breast tissues and breast cancer tissues (P < 0.05). The overall survival of breast cancer patients with higher MMP11 expression was shorter, and there were statistically significant results in breast cancer patients with Luminal A, Luminal B, Her-2 overexpression and node-negative breast cancer (P < 0.05). At the single-cell level, the expression of MMP11 gene was significantly negatively correlated with epidermal-to-mesenchymal transition and proliferative effects (r = −0.60, −0.54, P < 0.05). Conclusion: MMP11 is highly expressed in breast cancer patients, and the expression level is related to the survival prognosis of patients, and it is speculated that MMP11 is a potential target for the diagnosis and treatment of breast cancer.