Abstract PR08: Higher expression of SATB2 gene in hepatocellular carcinoma of African American patients determines aggressiveness phenotypes than those in Caucasian Americans

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Abstract In the US, hepatocellular carcinoma (HCC) incidence has tripled over the past two decades. This trend indicates that social determinants, genetic and environmental factors are driving the epidemic at the population level. Furthermore, the disease has disproportionately affected minority and disadvantaged populations. SATB2 (special AT-rich binding protein-2), a transcription factor and epigenetic regulator, influences gene expression both by modulating chromatin architecture and by functioning as a transcriptional co-factor. SATB2 is highly expressed in embryonic stem cells and progenitor cells, whereas its expression is low or absent in human normal liver tissues. We have recently demonstrated that overexpression of SATB2 can transform normal epithelial cells to cancer stem-like cells in pancreatic, colorectal and breast cancer models, and the expression of SATB2 was significantly higher in cancer tissues compared to normal tissues. The purpose of this study was to examine the expression of SATB2 gene in HCC from AA and CA patients and assess its oncogenic potential by measuring cell viability, epithelial-mesenchymal transition (EMT), stem cell markers and pluripotency maintaining factors in cancer stem cells (CSCs). We compared the expression of SATB2 in primary hepatocytes, Hep3b (from AA), HepG2 (from CA) and HCC CSCs. Hep3b (higher), HepG2 (lower) and CSCs (highest) expressed SATB2 protein, whereas human primary normal hepatocytes did not express SATB2. Knockout of SATB2 in CSCs by Crispr/Cas9 technique significantly inhibited the expression of SATB2 gene, stem cell markers (CD24, CD44 and CD133), pluripotency maintaining factors (cMyc, KLF4, SOX2 and OCT4), and EMT compared to NTC control group. The expression of SATB2 was significantly higher in HCC tissues than adjacent normal controls. Furthermore, the expression of SATB2 was significantly higher in HCC tissues derived from AA compared to those in CA. These data suggest that SATB2 is an oncogenic factor and its expression, which is higher in in HCC tissues derived from AA, may explain the disparity in HCC outcomes among AA. This abstract is also being presented as Poster B049. Citation Format: S.K. Roy, Y. Ma, D.M. Danos, S. Shankar, L. Miele, R.A. Scribner, R.K. Srivastava. Higher expression of SATB2 gene in hepatocellular carcinoma of African American patients determines aggressiveness phenotypes than those in Caucasian Americans [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 PR08.