Abstract Pancreatic cancer is expected to become the second leading cause of cancer-related deaths in the United States by 2030 (Weniger, Honselmann, Liss, 2018), while the limited knowledge about its pathophysiology leads to the current lack of accurate prognostic tool and satisfactory treatment. Transcription factor GATA6 is highlighted as an interesting target based on the TCGA dataset analysis of mutational burdens among 15 African American patients and 12 white patients with pancreatic cancer. A previous in vitro study revealed that GATA6 inhibited epithelial-mesenchymal transition through both direct transcriptional regulation and indirect regulation of other transcription factors (Martinelli et al., 2017). However, the correlation between GATA6 and pancreatic cancer prognosis has not been fully understood. In our study, we assessed the GATA6 protein expression levels using immunohistochemistry (IHC) of a tissue microarray from one white and four black patients. The phenotype of low GATA6 expression was only found in two of four black patients, while tumors with high GATA6 expression were found both in black and white patients. Noticeably, the patients with GATA6low phenotype demonstrated inferior survival compared to those with GATA6high phenotype, indicating GATA6 as a potential prognostic biomarker. A detailed study using more patient samples is ongoing. We also established two pancreatic cancer cell lines with specific GATA6 knockdown via the CRISPR/Cas9 method to continue investigating the role of GATA6 loss in the progress of the aggressive pancreatic cancer. Success in future work will potentially contribute to a useful prognostic tool as well as development of novel therapies for pancreatic cancer patients with GATA6low phenotype. Citation Format: Haoyu Tang, Anup Sharma, Ilke Nalbantoglu, Nesrin Hasan, Andre Levchenko, Nita Ahuja. GATA6 level is a prognostic biomarker for pancreatic cancer in African American patients [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C54.