Abstract C034: Differential gene expression according to ancestry in Hispanic/Latina women with luminal B breast cancer
Authors: Alvarado Joussette I. , Garai Jone , Li Li , Boe Adam J. , Cress Doug , Antonia Teresita , Teer Jamie , Miele Lucio , Zabaleta Jovanny 
Published: August 2020

Abstract
Background: Breast cancer (BC) is the second leading cause of cancer-related death in women. There is a lack of breast cancer studies showing the differential gene expression in minorities. We have previously found differences in gene expression according to ancestry in Hispanic/Latina women with BC. The goal of our study was to determine the differential gene expression between high and low European, African, and Native ancestries of Hispanic/Latina women with luminal B BC.
Methods: Breast cancer tissue samples were collected from the Moffitt Cancer Center (MCC) in Tampa, FL, and had been analyzed for ancestry informative markers (AIMs) as part of a collaboration between MCC and the University of Puerto Rico. The RNA was quantified, qualified, and used to prepare genomic libraries using regents and protocols from Illumina at the Translational Genomics Core, Stanley S. Scott Cancer Center, LSUHSC-New Orleans. Quality assessment showed close to 50% alignment in coding regions. Raw counts were normalized and used to perform differential gene expression analysis (p&lt;0.05 and fold change &gt;2.0) using DESeq2 in R-Studio between individuals with high and low European, African, and Native ancestral fractions. Heatmaps were used to compare the distribution of the samples visually based on ancestry fraction and the level of gene expression. We used the online tool Venny (http://bioinfogp.cnb.csic.es/tools/venny/) to identify significantly different genes that were uniquely expressed in each ancestral group or shared between them. In addition, we used online tools (http://xcell.ucsf.edu/) for cell infiltration analysis and the software MetaCore to identify possible pathways in which the differentially expressed genes may be involved.
Results: We found a significant inverse correlation between European and both African and Native American ancestries, and these clearly separated based on high and low ancestral fraction. Eighteen genes were shared between European and Native American ancestries, showing opposite expression between the ancestries, suggesting an ethnicity-associated expression. The expression of these genes was validated by real-time PCR. Interestingly, cBioportal analysis showed that ANO1, EPN3, PLAT, and TRPA1 genes are frequently amplified in breast cancer. Furthermore, one gene SPAG6 was commonly expressed among all ancestries with a positive correlation in Native ancestry and negative correlation in European ancestry. We found that African ancestry was associated with the infiltration on lymphocyte progenitors and type 2 macrophages. Meanwhile, European and Native ancestries correlated with type 2 lymphocytes and monocytes, respectively. Pathway analysis revealed possible activation of immune responses driven by genes significant in European and Native ancestries.
Conclusions: Overall, our data suggest that patients with luminal B breast cancer may have differential gene expression associated to ancestry, to gene abnormalities and differential immune responses.
Citation Format: Joussette I. Alvarado, Jone Garai, Li Li, Adam J. Boe, Doug Cress, Teresita Antonia, Jamie Teer, Lucio Miele, Jovanny Zabaleta. Differential gene expression according to ancestry in Hispanic/Latina women with luminal B breast cancer [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C034.