title: A pooled treatment-curated breast cancer gene-expression dataset

status: Public on Mar 09 2024

city: Brussels

first: Vinu

last: Jose

address: Rue Meylemeersch 90

country: Belgium

institute: Institut Jules Bordet – Université Libre de Bruxelles (ULB)

type:
Expression profiling by array
Third-party reanalysis

summary: Pre-clinical studies reported the immunogenic or immunomodulatory effects of traditional cancer therapies. However, the publicly available well-curated and harmonized breast cancer datasets, such as TCGA, METABRIC, and MetaGxBreast, lack careful curation of treatment regimens. Hence, limited exploration of the impact of therapies on the prognostic/predictive value of breast cancer biomarkers. Herein, we describe a pooled and treatment-curated gene-expression dataset to investigate the impact of treatments on the prognostic/predictive value of biomarkers. We searched the gene expression omnibus database to identify potential human breast cancer gene-expression datasets with anthracycline/taxane treatment. Published datasets with the detailed treatment regimen, clinical endpoint, clinical-pathological, and gene-expression data were extracted and harmonized. The dataset described herein would help researchers explore the interaction between gene-expression biomarkers and immunogenic/immunomodulatory treatments in breast cancer.

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Reanalysis of: GSM505470
Reanalysis of: GSM505471
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overall_design: Potential gene expression datasets with anthracycline/taxane-containing regimens were extracted from the GEO database on 31 July 2020. The GEO search identified 172 datasets (geo series). Among the 172 datasets identified, 136 datasets were discarded due to 1) non-breast tissue expression profiles, 2) no treatment/outcome/survival data, 3) GEO sub/super-series already selected, 4) non-compactable experimental design, 5) xenografts, and 6) unpublished study. In addition, eight datasets were further discarded due to 1) non-whole genome expression profiles, 2) missingness in gene expression data, and 3) a few common genes with the rest of the datasets. Among the remaining 28 datasets, 23 datasets (2982 samples) were from neoadjuvant settings, and five datasets (754 samples) were from adjuvant settings. Of note, four datasets among the final 23 neoadjuvant datasets have paired expression profiles from pre/mid/post-treatment tumor specimens (n=279). Processed expression values from selected 28 GEO datasets were merged using common genes represented in the different gene expression profiling platforms. Multiple dataset effect correction methods were compared to select the optimal one. The methods compared were 1) combat, 2) quantile, and 3) MAD-quantile. The combat method is designed initially to adjust the microarray dataset for any experiment batch effect. However, combat can also be used to correct dataset effects from the pooled dataset. Furthermore, the quantile method of pooling gene expression rescaled (gene-rescale: expression rescaling per gene) individual datasets is reported to eliminate the dataset effect. Finally, the MAD-quantile method integrates expression rescaling per sample (sample-rescale) with the above gene-rescaling method (quantile method), pooling sample-rescaled and gene-rescaled individual datasets. The quantile method seems superior to the others. The processed expression values given in the series matrix were corrected using the quantile method. The pooled expression matrix corrected using the different dataset-effect correction methods described above were given in the supplementary data and relevant QC metrics.

last: Venet

first: Laurence

last: Buisseret

first: Francoise

last: Rothe

first: Christos

last: Sotiriou