Tseng Ling-Ming, Chiu Jen-Hwey, Liu Chun-Yu, Tsai Yi-Fang, Wang Yun-Lin, Yang Chu-Wen, Shyr Yi-Ming
Comprehensive Breast Health Center & Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, No. 201, Sec. II, Shih-pei Road, Taipei, 112, Taiwan, ROC.
Department of Surgery, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
Breast Cancer Res Treat. 2017 Jun;163(2):241-254. doi: 10.1007/s10549-017-4195-7. Epub 2017 Mar 15.
"Precision medicine" is a concept that by utilizing modern molecular diagnostics, an effective therapy is accurately applied for each cancer patient to improve their survival rates. The treatment of triple-negative breast cancer (TNBC) remains a challenging issue. The aim of this study was to compare the molecular subtypes of triple-negative breast cancer (TNBC) between Taiwanese and Non-Asian women.
GEO Datasets for non-Asian (12 groups, n = 1450) and Taiwanese (3 groups, n = 465) breast cancer, including 617 TNBC, were acquired, normalized and cluster analyzed. Then, using TNBC cell lines of different subtypes, namely, MDA-MB-468 (basal-like1, BL1), MDA-MB-231 (mesenchymal stem like, MSL), BT-549 (mesenchymal, M), MDA-MB-453 (luminal androgen receptor, LAR), and DU4475 (immunomodulatory, IM), real-time PCR in triplicate for 47 genes signatures were performed to validate the specificity of these subtypes.
The results showed that the percentage of TNBC subtypes in non-Asian women, namely, BL1, BL2, IM, M, MSL, and LAR was 13.56, 8.91, 16.80, 20.45, 8.30, and 11.13%, respectively. When data from Taiwanese were normalized and clustered, five TNBC subtypes, namely, BL (8.94%), IM (13.82%), M (22.76%), MSL (30.89%), and LAR (23.58%), were classified. Real-time PCR validated the specificity of these subtypes. Besides, the presence of interaction between IM- and MSL-subtypes suggests the involvement of tumor microenvironment in TNBC subtype classification.
Our data suggested that there exist different presentations between non-Asian and Taiwanese TNBC subtypes, which provides important information when selection of therapeutic targets or designs for clinical trials for TNBC patients.
“精准医学”是一种利用现代分子诊断技术，针对每位癌症患者精准应用有效治疗方法以提高其生存率的理念。三阴性乳腺癌（TNBC）的治疗仍然是一个具有挑战性的问题。本研究的目的是比较台湾女性和非亚洲女性三阴性乳腺癌（TNBC）的分子亚型。
获取非亚洲（12组，n = 1450）和台湾（3组，n = 465）乳腺癌的GEO数据集，包括617例TNBC，进行标准化和聚类分析。然后，使用不同亚型的TNBC细胞系，即MDA-MB-468（基底样1型，BL1）、MDA-MB-231（间充质干细胞样，MSL）、BT-549（间充质型，M）、MDA-MB-453（腔面雄激素受体型，LAR）和DU4475（免疫调节型，IM），对47个基因特征进行一式三份的实时PCR检测，以验证这些亚型的特异性。
结果显示，非亚洲女性中TNBC亚型的百分比，即BL1、BL2、IM、M、MSL和LAR分别为13.56%、8.91%、16.80%、20.45%、8.30%和11.13%。对台湾的数据进行标准化和聚类后，分类出五种TNBC亚型，即BL（8.94%）、IM（13.82%）、M（22.76%）、MSL（30.89%）和LAR（23.58%）。实时PCR验证了这些亚型的特异性。此外，IM亚型和MSL亚型之间存在相互作用，提示肿瘤微环境参与了TNBC亚型分类。
我们的数据表明，非亚洲和台湾TNBC亚型存在不同表现，这为TNBC患者选择治疗靶点或设计临床试验提供了重要信息。
