Abstract
Background“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.MethodsGEO 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.ResultsThe 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.ConclusionOur 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.
Highlights
Precision medicine has become an important emerging approach to the diagnosis, treatment, and prevention of disease, especially cancers; it takes into account the individual variability of each person in terms of genes, environment, and lifestyle
The results showed that the percentage of triple-negative breast cancer (TNBC) subtypes in non-Asian women, namely, BL1, BL2, IM, M, mesenchymal stem like (MSL), and luminal androgen receptor positive (LAR) was 13.56, 8.91, 16.80, 20.45, 8.30, and 11.13%, respectively
Breast Cancer Res Treat (2017) 163:241–254 presence of interaction between IM- and MSL-subtypes suggests the involvement of tumor microenvironment in TNBC subtype classification
Summary
Precision medicine has become an important emerging approach to the diagnosis, treatment, and prevention of disease, especially cancers; it takes into account the individual variability of each person in terms of genes, environment, and lifestyle. Owing to tumor heterogeneity caused by cell phenotype diversity, different approaches to treatment and prognosis have been shown to be highly correlated with the intrinsic subtypes of the breast cancer [3]. More investigations have targeted TNBC tumor heterogeneity using gene ontology [8,9,10], therapeutic targets [11, 12], and using mRNA or long noncoding RNAs (lncRNAs) as diagnostic criteria [13]. The six subtype classification has been refined recently [14, 15], the variation in molecular classification of TNBC across various different populations remains to be elucidated
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