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| Status |
Public on Oct 30, 2019 |
| Title |
Transcriptional signatures derived from murine tumor-associated macrophages predict outcome in breast cancer patients |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Third-party reanalysis
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| Summary |
Macrophages are frequently the most abundant immune cells in murine and human cancers. Studies in various transgenic mouse tumor models have revealed pro-tumor functions of tumor-associated macrophages (TAMs), but despite their association with poor clinical outcome in human patients, molecular signatures for the prediction of clinical outcome in humans are still missingbeen demonstrated. Here we generated molecular signatures from F4/80+CD11b+ TAMs from two transgenic breast cancer models: K14cre;Cdh1flox/flox;Trp53flox/flox (KEP), which resembles human invasive lobular carcinoma (ILC) and MMTV-NeuT (NeuT), which resembles HER2-overexpressing breast cancer. Determination of truly specific TAM transcriptome signatures in breast cancer required relationship analysis with healthy mammary gland tissue macrophages (MTMs), since comparison with macrophages from tissues overestimated TAM-specific gene expression. Furthermore, translation of the TAM signatures to outcome prediction in patients required consideration of the breast cancer subtype. TAM signatures derived from the KEP, but not the NeuT model reliably predicted outcome in ILC patients. Collectively, we show that a transgenic mouse tumor model can be utilized to derive a TAM-based signature for human breast cancer outcome prediction and provide a generalizable strategy for determining and applying specific molecular signatures of immune cells to, in principle, any cancer provided the murine model reflects the human disease.
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| Overall design |
Analysis of changes in the expression of mRNAs in tow different murine breast cancer models.
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| Contributor(s) |
Tuit S, Salvagno C, Kapellos TS, Hau C, Seep L, Oestreich M, Klee K, de Visser KE, Ulas T, Schultze JL |
| Citation(s) |
31665635 |
| Submission date |
Feb 08, 2019 |
| Last update date |
Jan 29, 2020 |
| Contact name |
Joachim Schultze |
| E-mail(s) |
j.schultze@uni-bonn.de
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| Organization name |
LIMES (Life and Medical Sciences Center Genomics and Immunoregulation)
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| Department |
Genomics and Immunoregulation
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| Street address |
Carl-Troll-Strasse 31
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| City |
Bonn |
| State/province |
NRW |
| ZIP/Postal code |
53115 |
| Country |
Germany |
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| Platforms (1) |
| GPL18480 |
Illumina HiSeq 1500 (Mus musculus) |
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| Samples (44)
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| Relations |
| BioProject |
PRJNA521461 |
| SRA |
SRP184641 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE126268_norm_data.txt.gz |
3.3 Mb |
(ftp)(http) |
TXT |
| GSE126268_published_reanalyzed_samples_list.xlsx |
12.8 Kb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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