[关键词]
[摘要]
目的:探究铜死亡相关基因COX17在乳腺癌组织和细胞中的表达及其与肿瘤免疫细胞浸润、临床特征和患者预后的关系。方法:通过多种数据库数据分析COX17 在人体正常组织和泛癌组织与细胞中的表达及其与患者预后的关系、COX17 基因突变情况、COX17表达水平与肿瘤免疫微环境的相关性、COX17在浸润性乳腺癌中表达水平及其与患者临床病理特征的相关性、在乳腺癌细胞中COX17基因遗传突变及甲基化情况、COX17差异共表达基因的功能富集分析,构建COX17蛋白质相互作用网络及功能分析。采用免疫组化法检测COX17蛋白在国人乳腺癌组织中的表达以验证数据库分析结果。结果:COX17 mRNA广泛分布于全身组织中且在多数癌组织中呈高表达,COX17蛋白在乳腺癌等癌组织中呈高表达,COX17 mRNA表达水平明显影响乳腺癌等癌症患者的预后,COX17 基因在多种癌组织中突变频率高且其主要突变类型为错义突变、扩增和深度缺失,COX17mRNA表达水平与多种肿瘤的肿瘤纯度和多种免疫细胞浸润存在相关性,COX17蛋白水平与乳腺癌临床分期、病理分型、淋巴结转移、患者性别和年龄有关联。免疫组化法检测结果证实在国人乳腺癌组织中COX17蛋白也呈高表达,COX17基因在乳腺癌中遗传突变和修饰特征分别是截断突变和启动子区高度甲基化。COX17蛋白与ATOX1等多种蛋白表达相关且构成复杂的相互作用网络,COX17在乳腺癌中差异表达基因主要涉及氧化还原酶活性、蛋白翻译、氧化磷酸化及TNF信号通路等生物过程。结论:COX17在乳腺癌组织和细胞中呈高表达,且与癌组织的免疫细胞浸润和患者预后相关,COX17是临床治疗乳腺癌的潜在靶点。
[Key word]
[Abstract]
Objective: To explore the expression of COX17 in pan-cancerous tissues and its relationship with tumor immune cell infiltration and the prognosis of patients. Methods: The expressions of COX17 in human normal tissues and pan-cancerous tissues and its relationship with the prognosis of patients, the mutation of COX17 gene, the correlation between the expression level of COX17 and tumor immune microenvironment, the correlation between the expression level of COX17 in invasive breast cancer and the clinicopathological characteristics of patients, the genetic mutation and methylation of COX17 gene in breast cancer cells were analyzed, using a variety of public cancer database data. The functional enrichment analysis of the differentially co-expressed genes of COX17 in breast cancer, the construction of the protein interaction network of COX17 and the functional analysis were carried out.Finally, the expression of COX17 protein in breast cancer tissues of Chinese nationals was detected by immunohistochemistry to verify database analysis results. Results: COX17 mRNA is widely distributed in the whole body and highly expressed in most cancer tissues.COX17 protein is highly expressed in breast cancer and other cancer tissues. The expression level of COX17 mRNA significantly affects the prognosis of patients with breast cancer and other cancers. COX17 gene has a high mutation frequency in a variety of cancer tissues, and its main mutation types are missense mutation, amplification and deep deletion. The expression level of COX17 mRNA was correlated with tumor purity and immune cell infiltration in a variety of tumors. The expression level of COX17 was correlated with the clinical stage, the pathological type, lymph node metastasis, the gender and age of patients. Immunohistochemical detection results confirmed that COX17 protein was also highly expressed in the breast cancer tissues of Chinese nationals. The genetic mutation and modification characteristics of COX17 gene in breast cancer were truncation mutation and promoter hypermethylation, respectively,COX17 protein is related to the expressions of ATOX1 and other proteins and forms a complex interaction network. The differentially expressed genes of COX17 in breast cancer mainly involve biological processes such as oxidoreductase activity, protein translation,oxidative phosphorylation and TNF signaling pathway. Conclusion: COX17 is highly expressed in most pan cancers and is related to the immune cell infiltration of a variety of tumors and the prognosis of patients. COX17 is a potential target for clinical treatment of breast cancer.
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[基金项目]
新疆维吾尔自治区自然科学基金(No. 2023D01C40)