乳腺癌变过程中Pim1和Notch1差异性表达的临床价值

熊世双; 陈晓文; 穆亚男; 张德瑞; 蒋金芳; 李军; 曹玉文

doi:10.3971/j.issn.1000-8578.2020.19.1434

乳腺癌变过程中Pim1和Notch1差异性表达的临床价值

Clinical Value of Differential Expression of Pim1 and Notch1 During Carcinogenesis of Breast Cancer

摘要

摘要:
目的探讨Pim1和Notch1在乳腺组织中差异性表达的临床意义及与预后的关系。
方法 qRT-PCR、免疫组织化学法和数据库检测评估Pim1、Notch1 mRNA和蛋白在乳腺癌旁正常组织、普通型导管增生、导管原位癌和浸润性导管癌中的表达水平，分析Pim1和Notch1表达与乳腺癌患者临床病理参数的关系，Kaplan-Meier Plotter数据库发掘Pim1和Notch1在乳腺癌预后中的价值。
结果乳腺癌组织中Pim1 mRNA水平升高，Pim1蛋白表达明显降低；Pim1 mRNA与淋巴结转移和TNM晚期密切相关，Pim1蛋白在淋巴结转移及高分级患者中表达显著减少，其低表达的患者无复发生存期更短(P=0.000)。Notch1 mRNA和蛋白在乳腺癌中显著高表达，Notch1 mRNA与淋巴结转移、高分级和晚分期明显相关，Notch1蛋白在淋巴结转移组中表达显著升高，其高表达患者总生存时间减少(P=0.025)。Pim1和Notch1蛋白表达在乳腺癌中负相关(r=-0.385，P=0.001)。
结论 Pim1低表达和Notch1高表达可能是促进乳腺癌发生发展及预后不良的危险因素，可能成为评估乳腺癌潜在生物标志物。

Abstract:
Objective To investigate the differential expression levels of Pim1 and Notch1 in breast tissues and their clinical and prognostic significance.
Methods qRT-PCR, immunohistochemistry and databases were used to detect the mRNA and protein levels of Pim1 and Notch1 genes in adjacent normal breast tissues (ANBT), usual ductal hyperplasia (UDH), ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). The relation between Pim1/Notch1 expression and the clinicopathological parameters of breast cancer patients was analyzed. The prognostic value of Pim1 and Notch1 protein in breast cancer was evaluated by Kaplan-Meier Plotter databases.
Results The expression of Pim1 mRNA in breast cancer tissues was increased. The expression of Pim1 protein in the breast cancer tissues was significantly decreased. The expression of Pim1 mRNA was markedly associated with lymph node metastasis and advanced TNM stage. The expression of Pim1 protein was significantly decreased in the patients with lymph node metastasis or histological grade 3. The patients with low expression of Pim1 had a shorter relapse-free survival (P=0.000). The expression of Notch1 mRNA and protein in breast cancer were higher than those in normal breast tissues. Notch1 mRNA was closely related to the lymph node metastasis, high grade and advanced stage. Notch1 protein expression in lymph node metastasis group had markedly increased. The overall survival time of patients with high level of Notch1 was shorter (P=0.025). The protein levels of Pim1 and Notch1 were negatively correlated in breast cancer tissues (r=-0.385, P=0.001).
Conclusion Low Pim1 expression and high Notch1 expression may promote the carcinogenesis and progression of breast cancer and may be risk factors for poor prognosis. Pim1 and Notch1 may be used as potential biomarkers for clinical evaluation of breast cancer patients.

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