The role of genetic ancestry on the expression profiles and function of immune cells in individuals with aggressive colorectal subtypes
Candy Promprasert
Mentors: Deborah de la Caridad Delgado Herrera (1,2), Tingting Qin (3), Lucia Martinez Cruz (1,2), Siddhi Patil (1,2), Gregory T. Wolf (3) Anju Duttargi (1,2), Christina Lefante (5), Mei-Chin Hsieh (5), Esmael Besufikad, Nisha D’Silva (3,4,6), Maureen A. Sartor (3,6), Ernest Adjei, Binfeng Lu, Elena Martinez Stoffel, Laura Rozek (1,2) and Batsirai Mabvakure (1); 1. Cancer Prevention and Control Program, Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA; 2. School of Medicine, Department of Oncology, Georgetown University, Washington, DC, USA; 3. University of Michigan Medical Center, 1150 West Medical Center Drive, Ann Arbor, Michigan; 4. University of Michigan School of Dentistry, Ann Arbor, Michigan; 5. School of Public Health, Epidemiology Program, Louisiana State University Health Sciences Center, New Orleans, LA; 6. University of Michigan Rogel Comprehensive Cancer Center, Ann Arbor, Michigan.
Date/Time: August 23rd, 2024 at 1:40pm.
Abstract: Colorectal cancer ranks as the third most prevalent cancer worldwide, with over 1.9 million new cases annually. In 2023, the United States recorded an estimated 153,020 new cases of colorectal cancer, resulting in 52,550 deaths from the disease. African Americans face a 20% higher risk of developing colorectal cancer and exhibit a 5-year survival rate that is 40% lower compared to other populations.
The diversity, function, and expression profile of immune cells, significantly influence a patient’s response to cancer treatment. This study aims to explore the impact of genetic ancestry on the expression profiles and functions of immune cells among individuals with aggressive colorectal subtypes. The goal is to advance tailored treatment strategies for diverse population groups, thereby enhancing treatment outcomes.
The study will utilize samples obtained from colorectal cancer patients representing individuals of African descent as well as non-Hispanic white descent. These samples will be collected from several collaborative study sites in Washington DC., Michigan and Louisiana. To broaden the genetic background of African ancestry in the study, we will also include samples collected from our partner study sites in Ethiopia and Ghana.
RNA was extracted using the Qiagen RNA/DNA extraction kit, from 141 Formalin-Fixed Paraffin Embedded colorectal cancer tumors. The RNA has been sequenced (bulk RNA sequencing), and my study will perform bioinformatics analyses on the sequences to determine the genetic ancestry of the individuals and the colorectal cancer subtypes.
Four samples will be selected for single-cell sequencing, that have varying levels of African allele frequencies ranging from the highest frequency of African alleles to the lowest (non-Hispanic sample). Library preparation for single-cell RNA sequencing will be conducted using the 10X Genomics Chromium X instrument. Subsequently, bioinformatics analyses will be performed using CellRanger and Seraut in R to characterize different immune cell types, discern their expression profiles, and examine how genetic ancestry influences their function during colorectal cancer progression.
The preliminary findings indicate that certain genes exhibit a higher mutational frequency in African tumor samples compared to non-Hispanic white samples. Specifically, the DLC1 gene showed a differential mutational profile across various genetic ancestries and locations, with African American individuals displaying a higher number of mutations compared to non-Hispanic White individuals in Washington, DC. No DLC1 mutations were observed in samples from Ethiopia or Michigan. These 45 results underscore the importance of considering genetic ancestry in mutational studies, potentially 46 informing targeted treatments and improving outcomes in colorectal cancer therapy.