2. Academic Validation
  3. A high-risk luminal A dominant breast cancer subtype with increased mobility

A high-risk luminal A dominant breast cancer subtype with increased mobility

  • Breast Cancer Res Treat. 2019 Jun;175(2):459-472. doi: 10.1007/s10549-019-05135-w.
Liping Guo 1,  Guoji Chen 2,  Wen Zhang 3,  Lulin Zhou 1,  Ting Xiao 1,  Xuebing Di 1,  Yipeng Wang 4,  Lin Feng 5,  Kaitai Zhang 6
Affiliations

Affiliations

  • 1 State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • 2 Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • 3 Department of Immunology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
  • 4 Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. wangyi-82@126.com.
  • 5 State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. fenglin@cicams.ac.cn.
  • 6 State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China. zhangkt@cicams.ac.cn.
PMID: 30778902 DOI: 10.1007/s10549-019-05135-w
Abstract

Purpose: Breast Cancer is a heterogeneous disease, and although advances in molecular subtyping have been achieved in recent years, most subtyping strategies target individual genes independent of one another and primarily concentrate on proliferative markers. The contributions of biological processes and immune patterns have been neglected in breast Cancer subtype stratification.

Methods: We performed a gene set variation analysis to simplify the information on biological processes using hallmark terms and to decompose immune cell data using the immune cell gene terms on 985 breast invasive ductal/lobular carcinoma RNAseq samples in the TCGA database.

Results: The samples were gathered into three clusters following implementation of the t-SNE and DBSCAN algorithms and were categorized as 'hallmark-tsne' subtypes. Here, we identified a high-risk luminal A dominant breast Cancer subtype (C3) that displayed increased motility, Cancer stem cell-like features, a higher expression of hormone/luminal-related genes, a lower expression of proliferation-related genes and immune dysfunction. With regard to immune dysfunction, we observed that the motility-increased C3 subtype exhibited high granulocyte colony stimulating factor (G-CSF) expression accompanied by neutrophil aggregation. Cancer cells that produce high levels of G-CSF can stimulate neutrophils to form neutrophil extracellular traps, which promote Cancer cell migration. This finding sheds LIGHT on one potential explanation for why the C3 subtype correlates with poor prognosis.

Conclusions: The hallmark-tsne subtypes confirmed again that even the luminal A subtype is heterogeneous and can be further subdivided. The biological processes and immune heterogeneity of breast Cancer must be understood to facilitate the improvement of clinical treatments.

Keywords

Biology process; Breast cancer classification; Immune pattern; NETs; t-SNE.

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