Abstract B059: African American pancreatic cancer microRNAs profile to identify links to drug resistance and tumor progression

Abstract

Abstract Pancreatic cancer is a deadly disease with only 8% of the patients surviving 5 years (1). Recent data published for African Americans (AA) showed that this population has the highest death rate and shortest survival of any racial/ethnic group in the US for most cancers (2). The causes of this disparity are unknown; some of them may be socioeconomic as well as barriers to high-quality cancer prevention, early detection, and treatment information and services. It is clear that there is a gap between AA and Caucasian Americans (CA) concerning the development and death from pancreatic cancer. We hypothesize that there also are molecular differences in the tumors from AA and CA patients that contribute to this disparity. Importantly, The Cancer Genome Atlas (TCGA) numbers for pancreatic cancer reveals that only 7 out of 185 cases of pancreatic cancer are from African American patients. This clearly shows a prominent under-representation of tumor-related genetic information for the AA population. MicroRNAs (miRNAs) are able to regulate dozens of targets, especially those involved in cancer, making them a potential tool to study differences between populations. It is known that patients develop drug resistance against gemcitabine and one factor could be due to differential expression of miRNAs (3). The analysis of potential miRNA differences in AA and CA tumors would be a starting point to study the function(s) and mechanisms to understand the gap between these populations. We analyzed the tumor miRNAs expression of the TCGA 7 AA patients and compared the expression with 10 CA patients from TCGA to understand the main differences in expression between the two sets of samples. Using R studio, we found 26 miRNAs significantly different between CA and AA tumors. Some of them are involved in pathways related with tumor progression, cell invasion and tumor growth. We are interested in miRNAs involved in upregulating drug resistance against gemcitabine such as miR21, miR 155, or miR 196 as well as those miRNAs that dowregulate resistance to treatment like miR148, miR200 or miR34. Importantly, these miRNAs have been defined only in CA pancreatic tumor samples. We are collecting retrospective pancreatic cancer cases at SUNY Downstate Medical Center and Kings County Hospital Center to study the expression of miRNAs using Illumina technology in our AA population in Brooklyn, NY. These tissues will be matched for age, gender, body mass index, and for stage and site of disease to the best of our ability. Adjacent normal tissues will serve as standard controls. We will use CA PDAC cases from TCGA for comparison. This work is in progress. In conclusion, we found in our analysis 26 miRNAs differentially expressed between AA and CA using TCGA data. We expect to see a difference in expression of miRNAs using samples from our patient population. In addition, we are interested to see if our patients have a different expression pattern of miRNAs related to drug resistance and if this could explain the poor response often seen in AA PDAC patients. Citation Format: Maria Munoz-Sagastibelza, Mohamed Alshal, Sayed Imtiaz, Jenny E. Paredes Sanchez, Mubarak Akadri, Raavi Gupta, Maksim Agaronov, Ellen Li, Jovanny Zabaleta, Laura Martello-Rooney. African American pancreatic cancer microRNAs profile to identify links to drug resistance and tumor progression [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 B059.