Gene Expression Analysis of Hormone-Receptor Positive Breast Cancer

Gene expression data and clinical information of the MD Anderson Cancer Center cohort [18 (link)] (Affymetrix U133A microarrays) was downloaded from the GEO repository (GSE25066). A total of 320 tumors were HR+/HER2− and patients received neoadjuvant chemotherapy and adjuvant endocrine treatment if HR+. HR positivity was defined as any number of stained cells. We applied an additional filter based on gene expression of ESR1 (probeset 205225_at) based on its bimodal distribution (> 10.45). In total, 267 patients met these criteria. Additional file 3: Table S2 lists the patient characteristics. HLA-A, HLA-B, and HLA-C metagenes were calculated as mean expression of the respective probesets (HLA-A: 215313_x_at, 213932_x_at; HLA-B: 211911_x_at, 209140_x_at, 208729_x_at, HLA-C: 208812_x_at, 216526_x_at, 214459_x_at, 211799_x_at). Unsupervised cut-offs were chosen by assigning the same fraction of cases to the groups with high (60%) and low (40%) expression as in the GeparTrio dataset (HLA-A > 14.24, HLA-B > 13.63, and HLA-C > 13.69). Probesets 205225_at (estrogen receptor 1) and 208079_s_at (Aurora kinase A) were used to evaluate their association with HLA-A. Immune cell metagenes were calculated as the mean expression of cell-type-specific genes [16 (link)].

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Sinn B.V., Weber K.E., Schmitt W.D., Fasching P.A., Symmans W.F., Blohmer J.U., Karn T., Taube E.T., Klauschen F., Marmé F., Schem C., Stickeler E., Ataseven B., Huober J., von Minckwitz G., Seliger B., Denkert C, & Loibl S. (2019). Human leucocyte antigen class I in hormone receptor-positive, HER2-negative breast cancer: association with response and survival after neoadjuvant chemotherapy. Breast Cancer Research : BCR, 21, 142.

Publication 2019

U133A microarrays

Adjuvant Aurora kinase a Cancer Cell type Endocrine Estrogen receptor 1 Gene expression Genes Her2 Hla b Hla c Microarrays Neoadjuvant chemotherapy Patient Tumors

Corresponding Organization : Humboldt-Universität zu Berlin

Other organizations : German Breast group, Universitätsklinikum Erlangen, The University of Texas MD Anderson Cancer Center, University Hospital Frankfurt, Goethe University Frankfurt, German Cancer Society, University Hospital Heidelberg, Heidelberg University, University Hospital Schleswig-Holstein, University of Lübeck, RWTH Aachen University, Kliniken Essen-Mitte, University Hospital Ulm, Martin Luther University Halle-Wittenberg

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Variable analysis

independent variables

Expression of HLA-A, HLA-B, and HLA-C metagenes
Expression of estrogen receptor 1 (probeset 205225_at)
Expression of Aurora kinase A (probeset 208079_s_at)

dependent variables

Tumor characteristics of HR+/HER2− breast cancer patients who received neoadjuvant chemotherapy and adjuvant endocrine treatment

control variables

Gene expression data and clinical information of the MD Anderson Cancer Center cohort (Affymetrix U133A microarrays, GSE25066)
Patients with HR+ (any number of stained cells) and ESR1 expression (> 10.45)
Immune cell metagenes calculated using cell-type-specific genes

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