Lai Jianguo, Deng Shuxuan, Cao Jiyuan, Ren Yongqi, Xu Zanmei, Qi Xiaofang, Xu Mian, Liao Ning
Department of Breast Cancer, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China.
Shantou University Medical College, Shantou, Guangdong, China.
Discov Oncol. 2024 Sep 6;15(1):413. doi: 10.1007/s12672-024-01261-0.
Trop2, a cell membrane glycoprotein, is overexpressed in almost all epithelial cancers. This study aimed to explore the mutational characteristics and significance of Trop2 in breast cancer (BC).
Patients diagnosed with BC (n = 77) were enrolled to investigate expression level and clinical characteristics of Trop2. Database of cBioPortal and Kaplan-Meier Plotter were used to evaluate the effects of Trop2 (TACSTD2) genomic ateration and mRNA expression levels on disease-free survival (DFS) and relapse-free survival (RFS), respectively. Based on next generation sequencing analysis, the Trop2 mutation characteristics of BC patients were deeply depicted. In addition, Trop2 expression, mutation and methylation signature associated with Trop2 mutations were analyzed.
Trop2 mutation and high expression of Trop2 were predictive biomarker for shorter DFS and RFS in BC. The positive rate of Trop2 expression in these 77 BC patients was 96.1% (74/77). Based on the Trop2 expression level, the patients were classified into Trop2 negative group, medium expression group and high expression group. The mutation frequencies of MAP3K1, NOTCH2, PTEN and MAGI2 were significantly higher in Trop2 medium expression group than high expression group. Moreover, we investigated the effect of the Trop2 mutations on other genes, including co-expressed genes, differentially mutated genes, differentially expressed genes, gene methylation and phosphorylation. We found that MED8, DPH2, KDM4A, EBNA1BP2, USP1, IPO13, CGAS, PRKAA2, NCOA7, ASCC3 and ABRACL were differentially expressed, mutated and methylated between Trop2 mutation group and wild group.
MAP3K1, NOTCH2, PTEN and MAGI2 mutations were significantly different between Trop2 medium expression and Trop2 high expression BC patients. The effects of Trop2 mutation on the expression, variation, methylation, and phosphorylation of other genes were comprehensively revealed. High expression level of Trop2 and Trop2 mutation were predictive biomarker for poor prognosis and targeted therapy in BC.
Trop2是一种细胞膜糖蛋白，在几乎所有上皮癌中均过度表达。本研究旨在探讨Trop2在乳腺癌（BC）中的突变特征及意义。
纳入77例确诊为BC的患者，研究Trop2的表达水平及临床特征。利用cBioPortal数据库和Kaplan-Meier Plotter分别评估Trop2（TACSTD2）基因改变和mRNA表达水平对无病生存期（DFS）和无复发生存期（RFS）的影响。基于二代测序分析，深入描绘BC患者的Trop2突变特征。此外，分析了Trop2表达、突变及与Trop2突变相关的甲基化特征。
Trop2突变和Trop2高表达是BC患者DFS和RFS缩短的预测生物标志物。这77例BC患者中Trop2表达阳性率为96.1%（74/77）。根据Trop2表达水平，将患者分为Trop2阴性组、中等表达组和高表达组。Trop2中等表达组中MAP3K1、NOTCH2、PTEN和MAGI2的突变频率显著高于高表达组。此外，我们研究了Trop2突变对其他基因的影响，包括共表达基因、差异突变基因、差异表达基因、基因甲基化和磷酸化。我们发现MED8、DPH2、KDM4A、EBNA1BP2、USP1、IPO13、CGAS、PRKAA2、NCOA7、ASCC3和ABRACL在Trop2突变组和野生组之间存在差异表达、突变和甲基化。
Trop2中等表达和高表达的BC患者之间，MAP3K1、NOTCH2、PTEN和MAGI2突变存在显著差异。全面揭示了Trop2突变对其他基因表达、变异、甲基化和磷酸化的影响。Trop2高表达和Trop2突变是BC患者预后不良和靶向治疗的预测生物标志物。
