Elevated Resistin Gene Expression in African American Estrogen and Progesterone Receptor Negative Breast Cancer

<div><p>Introduction</p><p>African American (AA) women diagnosed with breast cancer are more likely to have aggressive subtypes. Investigating differentially expressed genes between patient populations may help explain racial health disparities. Resistin, one such gene, is linked to inflammation, obesity, and breast cancer risk. Previous studies indicated that resistin expression is higher in serum and tissue of AA breast cancer patients compared to Caucasian American (CA) patients. However, resistin expression levels have not been compared between AA and CA patients in a stage- and subtype-specific context. Breast cancer prognosis and treatments vary by subtype. This work investigates differential resistin gene expression in human breast cancer tissues of specific stages, receptor subtypes, and menopause statuses in AA and CA women.</p><p>Methods</p><p>Differential gene expression analysis was performed using human breast cancer gene expression data from The Cancer Genome Atlas. We performed inter-race resistin gene expression level comparisons looking at receptor status and stage-specific data between AA and CA samples. DESeq was run to test for differentially expressed resistin values.</p><p>Results</p><p>Resistin RNA was higher in AA women overall, with highest values in receptor negative subtypes. Estrogen-, progesterone-, and human epidermal growth factor receptor 2- negative groups showed statistically significant elevated resistin levels in Stage I and II AA women compared to CA women. In inter-racial comparisons, AA women had significantly higher levels of resistin regardless of menopause status. In whole population comparisons, resistin expression was higher among Stage I and III estrogen receptor negative cases. In comparisons of molecular subtypes, resistin levels were significant higher in triple negative than in luminal A breast cancer.</p><p>Conclusion</p><p>Resistin gene expression levels were significantly higher in receptor negative subtypes, especially estrogen receptor negative cases in AA women. Resistin may serve as an early breast cancer biomarker and possible therapeutic target for AA breast cancer.</p></div

Functional Classification of Differentially Expressed Genes in Human Prostate Cancer According to PANTHER Protein Class (A) and Biological Process Gene Ontology Terms (B).

<p>(A) “Nucleic Acid Binding” includes RNA and DNA binding, nucleases, and helicases. “Transcription Factor” includes zinc finger, helix-turn-helix, high mobility group box, basic helix-loop-helix, and basic leucine zipper transcription factors; cofactors; and nuclear hormone receptors. “Hydrolase” refers to proteases, phosphatases, esterases, lipases, deaminases, phosphodiesterases, glycosidases, deacetylases, pyrophosphatases, glucosidases, galactosidases, and amylases. “Receptor” includes protein kinase receptors, nuclear hormone receptors, cytokine receptors, ligand-gated ion channels, and G-protein coupled receptors. “Enzyme Modulator” includes G protein, kinase, phosphatase, and protease modulators. (B) “Metabolic Process” features carbohydrate, cellular amino acid, lipid, protein, and nucleobase-containing compound metabolism; and the tricarboxylic acid cycle. “Cellular Process” categories are cell-cell signaling, cell cycle, growth and proliferation, cell component movement, and cytokinesis. “Biological Regulation” includes the regulation of apoptosis, metabolism, cell cycle, translation, catalytic activity, and homeostasis. “Developmental Process” categories are system, ectoderm, mesoderm, and endoderm development; cell differentiation; death; anatomical structure morphogenesis; embryo development; sex determination; and pattern specification processes. “Localization” includes transport proteins, protein and RNA localization processes.</p

Magnitude of gene expression differences between tumor and non-malignant human prostate cancer samples.

<p>In this one-dimensional scatter plot the magnitude of gene expression changes represented by log₂ fold ratios are shown. Each point represents a gene or transcript. Significantly differentially expressed genes and transcripts are shown as solid red diamonds.</p

Inter-racial comparison of resistin gene expression between Caucasian American and African American breast tumors by stage/menopause status.

<p>Inter-racial comparison of resistin gene expression between Caucasian American and African American breast tumors by stage/menopause status.</p

Intra-racial comparison of resistin gene expression of Caucasian American and African American breast tumors by stage/menopause status.

<p>Intra-racial comparison of resistin gene expression of Caucasian American and African American breast tumors by stage/menopause status.</p

Breast Cancer Patient Data from TCGA.

<p>Breast Cancer Patient Data from TCGA.</p

P-value of resistin gene expression between matched malignant and non-malignant breast samples.

<p>P-value of resistin gene expression between matched malignant and non-malignant breast samples.</p

Resistin gene expression in whole population breast tumors by stage and receptor status.

<p>Resistin gene expression in whole population breast tumors by stage and receptor status.</p

Resistin gene expression within Caucasian American and African American breast tumors by stage/receptor status.

<p>Resistin gene expression within Caucasian American and African American breast tumors by stage/receptor status.</p

Resistin gene expression between Caucasian American and African American breast tumors by stage/receptor status.

<p>Resistin gene expression between Caucasian American and African American breast tumors by stage/receptor status.</p