Sun Yu-Lu, Zhao Yi-Xin, Guan Yi-Nan, You Xin, Zhang Yin, Zhang Meng, Wu Hong-Yan, Zhang Wei-Jie, Yao Yong-Zhong
Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, People's Republic of China.
Medical School of Southeast University, Nanjing, Jiangsu Province, People's Republic of China.
Adv Ther. 2023 Sep;40(9):4004-4023. doi: 10.1007/s12325-023-02588-w. Epub 2023 Jul 9.
Lymph node metastasis is a cause of poor prognosis in breast cancer. Mass spectrometry-based proteomics aims to map the protein landscapes of biological samples and profile tumors more comprehensively. Here, proteomics was employed to identify differentially expressed proteins (DEPs) that were associated with lymph node metastasis.
Tandem mass tag (TMT) quantitative proteomic approaches were applied for extensive profiling of conditioned medium of MDA-MB-231 and MCF7 cell lines and serums of patients who did or did not have lymph node metastasis, and DEPs were analyzed by bioinformatics. Furthermore, potential secreted or membrane proteins MUC5AC, ITGB4, CTGF, EphA2, S100A4, PRDX2, and PRDX6 were selected for verification in 114 tissue microarray samples of breast cancer using the immunohistochemical method. The relevant data was analyzed and processed by independent sample t test, chi-square test, or Fisher's exact test using SPSS 22.0 software.
In the conditioned medium of MDA-MB-231 cell lines, 154 proteins were upregulated, while 136 were downregulated compared to those of MCF7. In the serum of patients with breast cancer and lymph node metastasis, 17 proteins were upregulated, and 5 proteins were downregulated compared to those without lymph node metastasis. Furthermore, according to tissue verification, CTGF, EphA2, S100A4, and PRDX2 were associated with breast cancer lymph node metastasis.
Our study provides a new perspective for the understanding of the role of DEPs (especially CTGF, EphA2, S100A4, and PRDX2) in the development and metastasis of breast cancer. They could become potential diagnostic and prognostic biomarkers and therapeutic targets.
淋巴结转移是乳腺癌预后不良的一个原因。基于质谱的蛋白质组学旨在描绘生物样本的蛋白质图谱，并更全面地分析肿瘤特征。在此，我们采用蛋白质组学来鉴定与淋巴结转移相关的差异表达蛋白（DEPs）。
采用串联质谱标签（TMT）定量蛋白质组学方法，对MDA-MB-231和MCF7细胞系的条件培养基以及有或无淋巴结转移的乳腺癌患者血清进行广泛分析，并通过生物信息学分析差异表达蛋白。此外，选择潜在的分泌蛋白或膜蛋白MUC5AC、ITGB4、CTGF、EphA2、S100A4、PRDX2和PRDX6，采用免疫组化方法在114例乳腺癌组织芯片样本中进行验证。使用SPSS 22.0软件，通过独立样本t检验、卡方检验或Fisher精确检验对相关数据进行分析和处理。
与MCF7细胞系相比，MDA-MB-231细胞系的条件培养基中有154种蛋白上调，136种蛋白下调。与无淋巴结转移的患者血清相比，有淋巴结转移的乳腺癌患者血清中有17种蛋白上调，5种蛋白下调。此外，经组织验证，CTGF、EphA2、S100A4和PRDX2与乳腺癌淋巴结转移相关。
我们的研究为理解差异表达蛋白（尤其是CTGF、EphA2、S100A4和PRDX2）在乳腺癌发生和转移中的作用提供了新的视角。它们可能成为潜在的诊断、预后生物标志物和治疗靶点。
