Abstract A039: Multi-omic analyses of pancreatic ductal adenocarcinoma patients of African ancestry

Abstract Pancreatic ductal adenocarcinoma (PDAC) ranks among the most aggressive malignancies globally, with a 5-year survival rate of only 13%. The incidence and associated mortality of PDAC in Sub-Saharan Africa are rising. Despite this, there is insufficient data available from patients of African ancestry to inform effective diagnostic and therapeutic modalities adequately. Several studies have demonstrated distinct clinical and molecular factors associated with patients of different ethnicities and geographical locations, suggesting the need to characterise the disease in our population. This study aims to comprehensively characterise our patient group using high-throughput technologies and bioinformatics to integrate the data adequately. We employed a multimodal approach, integrating multi-omic data with relevant clinicopathological data. Summarily, proteomic tissue analyses involved 78 FFPE PDAC tissues. DNA and Total RNA were subsequently extracted from a subset of 28 tissues (14 paired tumours and normal tissues), and whole-exome and RNA sequencing were performed, respectively. Furthermore, proteomics analyses were conducted on serum samples obtained from 63 PDAC and 62 Benign biliary pathology samples. We identified differentially expressed and mutated targets in our tumour samples compared with controls at both tumour and plasma levels. Interestingly, some of these targets appear unique to our patient group. For example, key targets and pathways linked to tumour aggressiveness and therapeutic resistance, such as extracellular matrix organisation, platelet activation and fibrosis-related pathways, were identified. Furthermore, we demonstrated distinct molecular subtypes within our patient group that could explain disease progression. The findings from this study have enhanced our understanding of tumour development in our patient population. Furthermore, the study helps address the disparities from the lack of representation of African patients, offering opportunities for improved and precise diagnostic and treatment strategies. Citation Format: Sinegugu Dubazana, Sharol Ngwenya, Nnenna Elebo, Phelelani Mpangase, Monde Ntwasa, Jones Omoshoro-Jones, Previn Naicker, Stefano Cacciatore, Sindisiwe Buthelezi, Emmanuel E. Nweke. Multi-omic analyses of pancreatic ductal adenocarcinoma patients of African ancestry [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr A039.