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| Status |
Public on May 19, 2015 |
| Title |
Gene-expression molecular subtyping of triple-negative breast cancer tumours: importance of immune response |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
Subtyping molecular characterization within a cohort of 107 TN-IHC by means of gene expression profiling
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| Contributor(s) |
Jézéquel P, Loussouarn D, Guérin-Charbonnel C, Campion L, Vanier A, Gouraud W, Lasla H, Guette C, Valo I, Verrièle V, Campone M |
| Citation(s) |
25887482 |
| |
| Submission date |
Jun 25, 2014 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Wilfried Gouraud |
| Organization name |
ICO - UMGC
|
| Department |
Integrated Center of Oncology René Gauducheau
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| Lab |
Omics Data Science Unit
|
| Street address |
bd Jacques Monod
|
| City |
Saint Herblain |
| ZIP/Postal code |
44805 |
| Country |
France |
| |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (107)
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| This SubSeries is part of SuperSeries: |
| GSE103091 |
Gene-expression molecular subtyping of triple-negative breast cancer tumors |
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| Relations |
| BioProject |
PRJNA253922 |
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