Dong Xubin, Lv Shihui, Gu Dianna, Zhang Xiaohua, Ye Zhiqiang
Department of Thyroid and Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Radiotherapy and Chemotherapy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Front Oncol. 2021 Jan 21;10:553628. doi: 10.3389/fonc.2020.553628. eCollection 2020.
The role of L Antigen Family Member 3 (LAGE3) in breast cancer (BC) has not been sufficiently studied. In this study, we explored the clinical value and biological functions of LAGE3 in BC. Comprehensive analysis of LAGE3 was carried out on The Cancer Genome Atlas, Molecular Taxonomy of Breast Cancer International Consortium and Gene Expression Omnibus datasets. Results showed that LAGE3 expression was higher in BC tissues than in normal breast tissues of public datasets and our local cohort. Moreover, its expression was higher in BC patients with larger tumor size, significant lymph node metastasis, higher tumor grade, and more advanced disease stage. High expression of LAGE3 was correlated with poor prognosis, and LAGE3 could independently predict survival of BC patients. Functional enrichment analysis revealed a correlation between LAGE3 expression and biochemical metabolism and immune-related terms and cancer-related pathways. Analysis of tumor microenvironment indicated that LAGE3 expression was associated with the immune cell infiltration and anti-cancer immunity cycle. LAGE3 expression was higher in triple-negative breast cancer (TNBC) compared to hormone receptor-positive BC, but not HER2-positive subtype. Suppression of LAGE3 expression inhibited the proliferation and induced apoptosis of TNBC cell lines. Besides, the down-regulation of LAGE3 attenuated the migration and invasion but reduced the expression level of epithelial-mesenchymal-transition related proteins in TNBC cell lines. In conclusion, this study demonstrated for the first time that LAGE3 promotes the progression of BC. Therefore, it may be a potential diagnostic and prognostic biomarker, as well as a treatment target for BC.
L抗原家族成员3（LAGE3）在乳腺癌（BC）中的作用尚未得到充分研究。在本研究中，我们探讨了LAGE3在BC中的临床价值和生物学功能。对癌症基因组图谱、国际乳腺癌分子分类联盟和基因表达综合数据库中的LAGE3进行了综合分析。结果显示，在公共数据集和我们本地队列中，BC组织中LAGE3的表达高于正常乳腺组织。此外，在肿瘤体积较大、有明显淋巴结转移、肿瘤分级较高及疾病分期较晚的BC患者中，其表达更高。LAGE3的高表达与预后不良相关，且LAGE3可独立预测BC患者的生存情况。功能富集分析显示LAGE3表达与生化代谢、免疫相关术语及癌症相关通路之间存在关联。肿瘤微环境分析表明，LAGE3表达与免疫细胞浸润和抗癌免疫周期相关。与激素受体阳性的BC相比，三阴性乳腺癌（TNBC）中LAGE3的表达更高，但在HER2阳性亚型中并非如此。抑制LAGE3表达可抑制TNBC细胞系的增殖并诱导其凋亡。此外，LAGE3的下调减弱了TNBC细胞系的迁移和侵袭能力，但降低了上皮-间质转化相关蛋白的表达水平。总之，本研究首次证明LAGE3促进BC的进展。因此，它可能是一种潜在的诊断和预后生物标志物，以及BC的治疗靶点。
