蛋白质精氨酸甲基转移酶1在乳腺癌组织中的表达及临床意义

Expression and clinical significance of protein arginine methyltransferase 1 in breast cancer

摘要

目的：探究蛋白质精氨酸甲基转移酶1（protein arginine methyltransferase 1，PRMT1）在乳腺癌组织中的表达及其临床意义。方法：利用TIMER3.0、GEPIA2和UALCAN等数据库分析PRMT1 mRNA在乳腺癌组织中的表达水平；采用组织芯片及免疫组化技术检测PRMT1蛋白在乳腺癌组织中的表达，并探讨其与乳腺癌临床病理特征之间的关系；使用OSdream在线工具对Gene Expression Omnibus（GEO）数据集进行生存分析以评估PRMT1表达水平与乳腺癌患者无复发生存期（recurrence-free survival，RFS）和无转移生存期（metastasis-free survival，MFS）之间的关系；通过受试者工作特征（receiver operating characteristic，ROC）曲线分析评估PRMT1诊断乳腺癌的价值。结果：多数据库生物信息学分析结果显示，与正常乳腺组织相比，PRMT1 mRNA在乳腺癌组织中的表达水平显著升高（P<0.01）；PRMT1 mRNA的表达水平与临床分期和淋巴结转移密切相关（P<0.01）。组织芯片的免疫组化检测结果显示，与癌旁组织相比，PRMT1蛋白在乳腺癌组织中显著高表达（P<0.01），并且PRMT1高表达与乳腺癌患者临床分期和淋巴结转移呈正相关（P<0.01）。生存分析结果显示，PRMT1高表达乳腺癌患者的RFS和MFS显著短于PRMT1低表达患者（P<0.05）。ROC曲线分析显示，曲线下面积为0.927（95% CI：0.887~0.967， P<0.001），在最佳截断值（1.167）处的灵敏度和特异度分别为82.5%和90.0%，说明PRMT1具有良好的乳腺癌诊断效能。结论：PRMT1在乳腺癌组织中高表达，PRMT1高表达与乳腺癌患者的晚期临床分期、淋巴结转移和不良预后相关。PRMT1具有良好的乳腺癌诊断效能，可作为乳腺癌诊断与预后评判的潜在生物标志物。

Abstract

Objective：To investigate the expression of protein arginine methyltransferase 1 (PRMT1) in breast cancer and to evaluate its clinical significance. Methods：Bioinformatics databases, including TIMER3.0, GEPIA2, and UALCAN, were utilized to analyze PRMT1 mRNA expression levels in breast cancer tissues. Tissue microarray and immunohistochemistry were employed to detect PRMT1 protein expression in breast cancer tissues and to explore its correlation with clinicopathological features. Survival analysis based on Gene Expression Omnibus (GEO) datasets using the OSdream online tool was performed to assess the association between PRMT1 expression levels and recurrence-free survival (RFS) and metastasis-free survival (MFS) in breast cancer patients. The diagnostic value of PRMT1 for breast cancer was evaluated by receiver operating characteristic (ROC) curve analysis. Results：Multi-database bioinformatics analysis revealed that, compared to normal tissues, PRMT1 mRNA expression was significantly elevated in breast cancer tissues (P<0.01). Elevated PRMT1 mRNA levels were closely associated with advanced clinical stage and lymph node metastasis (P<0.01). Immunohistochemical staining of tissue microarrays confirmed that PRMT1 protein expression was significantly higher in breast cancer tissues compared to adjacent normal tissues (P<0.01). High PRMT1 expression was positively correlated with advanced clinical stage and lymph node metastasis in breast cancer patients (P<0.01). Survival analysis indicated that breast cancer patients with high PRMT1 expression had a significantly shorter RFS and MFS compared to those with low PRMT1 expression (P<0.05). The receiver operating characteristic (ROC) curve analysis showed that the area under the curve (AUC) was 0.927 (95%CI: 0.887-0.967, P<0.001). At the optimal cutoff value of 1.167, the sensitivity and specificity were 82.5% and 90.0%, respectively, indicating robust diagnostic performance of PRMT1 for breast cancer. . Conclusion：PRMT1 is highly expressed in breast cancer tissues, and elevated PRMT1 expression is associated with advanced clinical stage, lymph node metastasis, and poor prognosis in breast cancer patients. PRMT1 demonstrates excellent diagnostic efficacy for breast cancer. Therefore, PRMT1 may serve as a potential biomarker for the diagnosis and prognostic evaluation of breast cancer.

关键词

乳腺癌 / 蛋白质精氨酸甲基转移酶1 / 免疫组化

Key words

breast cancer / protein arginine methyltransferase 1 / immunohistochemistry

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基金资助

国家自然科学基金(82373058)

国家自然科学基金(82072484)

国家级大学生创新训练计划(202510312050Z)