Transcriptomics

Dataset Information

38

Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response


ABSTRACT: Triple-negative (TN) breast cancers need to be refined in order to identify therapeutic subgroups of patients. We conducted an unsupervised analysis of microarray gene-expression profiles of 107 TN breast cancer patients and undertook robust functional annotation of the molecular entities found by means of numerous approaches including immunohistochemistry and gene-expression signatures. An 87 TN external cohort was used for validation. Fuzzy clustering separated TN tumours into three clusters: C1 (22.4%), C2 (44.9%) and C3 (32.7%). C1 patients were older (mean = 64.6 years) than C2 (mean = 56.8 years; P = 0.03) and C3 patients (mean = 51.9 years; P = 0.0004). Histological grade and Nottingham prognostic index were higher in C2 and C3 than in C1 (P < 0.0001 for both comparisons). Significant event-free survival (EFS) (P = 0.03) was found according to cluster membership: patients belonging to C3 had a better outcome than patients in C1 (P = 0.01) and C2 (P = 0.02). EFS analysis results were confirmed when our cohort was pooled with external cohort (n = 194; P = 0.01). Functional annotation showed that 22% of TN patients were not basal-like (C1). C1 was enriched in luminal subtypes and positive androgen receptor (luminal androgen receptor [LAR]). C2 could be considered as an almost pure basal-like cluster. C3, enriched in basal-like subtypes, but to a lesser extent, included 26% of claudin-low subtypes. Dissection of immune response showed that high immune response (HIR) and low M2-like macrophages were a hallmark of C3, and that these patients had a better EFS than C2 patients, characterized by low immune response (LIR) and high M2-like macrophages: P = 0.02 for our cohort, and P = 0.03 for pooled cohorts. We identified 3 subtypes of TN patients: LAR (22%), basal-like with LIR and high M2-like macrophages (45%) and basal-enriched with HIR and low M2-like macrophages (33%). We pointed out that macrophages and other immune effectors offer a variety of therapeutic targets in breast cancer, and particularly in TN basal-like tumours. Furthermore, we showed that CK5 antibody was better suited than CK5/6 antibody to subtype TN patients. Subtyping molecular characterization within a cohort of 107 TN-IHC by means of gene expression profiling

ORGANISM(S): Homo sapiens  

SUBMITTER: Catherine Guérin-Charbonnel   Isabelle Valo  Loïc Campion  Véronique Verrièle  Hamza Lasla  Mario Campone  Delphine Loussouarn  Pascal Jézéquel  Catherine Guette  Wilfried Gouraud  Antoine Vanier 

PROVIDER: E-GEOD-58812 | ArrayExpress | 2015-05-19

SECONDARY ACCESSION(S): GSE58812PRJNA253922

REPOSITORIES: GEO, ArrayExpress

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Publications

Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response.

Jézéquel Pascal P   Loussouarn Delphine D   Guérin-Charbonnel Catherine C   Campion Loïc L   Vanier Antoine A   Gouraud Wilfried W   Lasla Hamza H   Guette Catherine C   Valo Isabelle I   Verrièle Véronique V   Campone Mario M  

Breast cancer research : BCR 20150320


Triple-negative breast cancers need to be refined in order to identify therapeutic subgroups of patients.We conducted an unsupervised analysis of microarray gene-expression profiles of 107 triple-negative breast cancer patients and undertook robust functional annotation of the molecular entities found by means of numerous approaches including immunohistochemistry and gene-expression signatures. A triple-negative external cohort (n=87) was used for validation.Fuzzy clustering separated triple-neg  ...[more]

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