Heterogeneous tumor microenvironment in pancreatic ductal adenocarcinoma: An emerging role of single-cell analysis

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies in the world, for which the mortality is almost as high as the disease incidence and is predicted to be the second-highest cause of cancer-related deaths by 2030. These cancerous tumors consist of diversified gene expressions within the different cellular subpopulations that include neoplastic ductal cells, cancer-associated fibroblasts, and immune cells, all of which collectively facilitate cellular heterogeneity in the PDAC tumor microenvironment (TME). Active intratumoral interaction within the cell populations in TME induces the proliferation of cancerous cells, accounting for tumorigenesis and rapid metastasis. Methods: This review will focus on novel findings uncovering PDAC heterogeneity in different cellular subpopulations using single-cell RNA-sequencing (scRNA-seq) and other single-cell analysis technologies. It will further explore the emerging role of single-cell technologies in assessing the role of different subpopulations of neoplastic ductal cells, cancer-associated fibroblasts, and immune cells in PDAC progression. Results and Conclusion: The application of scRNA-seq in PDAC has started to unveil associations between disease progression and heterogeneity in pancreatic TME and could influence future PDAC treatment. Recent advances in scRNA-seq have uncovered comprehensive analyses of heterogeneous ecosystems present within the TME. These emerging findings underpins further need for a more in-depth understanding of intratumoral heterogeneity in the PDAC microenvironment.