高 RRM2 表达预示着某些特定类型乳腺癌的不良预后。
High RRM2 expression has poor prognosis in specific types of breast cancer.
机构信息
Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Endocrinology, Hubei No. 3 People's Hospital of Jianghan University, Wuhan, China.
出版信息
PLoS One. 2022 Mar 15;17(3):e0265195. doi: 10.1371/journal.pone.0265195. eCollection 2022.
BACKGROUND
RRM2 plays an important role in different malignant tumors, but there are few studies in breast cancer. Public databases were used to analyze the expression of RRM2 in breast cancer and its prognostic value.
MATERIALS AND METHODS
A total of 2,509 breast cancer samples were downloaded from the METABRIC database. The relationship between RRM2 expression and clinical pathology was evaluated. Using the BCIP database and real-time-PCR, and western blotting, RRM2 mRNA and protein expression of RRM2 in breast cancer tissues and cell lines were evaluated. Univariate and multivariate analysis defined independent prognostic factors that affected the overall survival of patients with breast cancer. The Kaplan-Meier method was used to study the relationship between the high expression of RRM2 and overall survival and distant metastasis-free survival (DMFS) of breast cancer patients. Finally, We performed Gene Set Enrichment Analysis (GSEA) and obtained the relevant pathways associated with high expression of RRM2 potentially influencing breast cancer progression.
RESULTS
RRM2 expression was significantly correlated with age, tumor size, grade, menopausal status, molecular typing, ER, PR, and Her-2 of patients with breast cancer(P<0.05). Univariate and multivariate regression analysis showed that RRM2, the number of positive lymph nodes, ER, Her-2, tumor size, and tumor stage can be used as independent prognostic factors for overall survival of patients with breast cancer. Kaplan-Meier analysis showed that in patients with Luminal A and Normal like breast cancers and Stage1 and stage2 breast cancers, patients with high expression of RRM2 had worse overall survival and DMFS. The analysis of the GSEA pathway showed that RRM2 is mainly enriched in the ERBB signaling pathway and other pathways.
CONCLUSION
The high expression of RRM2 has a worse prognosis in patients with breast cancer with specific features. It can be used as a biomarker for the prognosis of breast cancer.
背景
RRM2 在不同的恶性肿瘤中发挥着重要作用，但在乳腺癌中的研究较少。本研究利用公共数据库分析 RRM2 在乳腺癌中的表达及其预后价值。
材料与方法
从 METABRIC 数据库中下载了 2509 例乳腺癌样本。评估 RRM2 表达与临床病理的关系。利用 BCIP 数据库和实时 PCR、western blot 检测 RRM2 在乳腺癌组织和细胞系中的 mRNA 和蛋白表达。单因素和多因素分析定义了影响乳腺癌患者总生存的独立预后因素。Kaplan-Meier 法用于研究 RRM2 高表达与乳腺癌患者总生存和无远处转移生存（DMFS）的关系。最后，我们进行了基因集富集分析（GSEA），并获得了与 RRM2 高表达相关的潜在影响乳腺癌进展的相关通路。
结果
RRM2 表达与乳腺癌患者的年龄、肿瘤大小、分级、绝经状态、分子分型、ER、PR、Her-2 显著相关（P<0.05）。单因素和多因素回归分析显示，RRM2、阳性淋巴结数、ER、Her-2、肿瘤大小和肿瘤分期可作为乳腺癌患者总生存的独立预后因素。Kaplan-Meier 分析显示，在 Luminal A 和正常样乳腺癌以及 1 期和 2 期乳腺癌患者中，RRM2 高表达患者的总生存和 DMFS 更差。GSEA 通路分析显示，RRM2 主要富集在 ERBB 信号通路和其他通路。
结论
具有特定特征的乳腺癌患者中 RRM2 的高表达预示着更差的预后，可作为乳腺癌预后的生物标志物。
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