Single-cell sequencing reveals heterogeneity between pancreatic adenosquamous carcinoma and pancreatic ductal adenocarcinoma with prognostic value

Abstract

Pancreatic adenosquamous carcinoma (ASPC) is a rare subtype of pancreatic cancer with lethal malignancy, and few studies have focused on the heterogeneity of ASPC. Here, we performed a single-cell sequencing procedure on pancreatic tumor tissue from an ASPC patient and a patient with high-grade intraductal papillary mucinous neoplasm (IPMN). Through the combined analysis of single-cell sequencing data from five pancreatic ductal adenocarcinoma (PDAC) patients, one IPMN patient, and one ASPC patient in a public database, we identified 11 main types of cells, including macrophages, B cells, cancer stem cells, ductal cells, fibroblasts, endo/stellate cells, neutrophils, acinar cells, T cells, natural killer (NK) cells, dendritic cells, and mast cells. Then, the different characteristics and differentiation paths of the immune microenvironment among IPMN, ASPC, and PDAC in macrophages, T cells, and cancer-associated fibroblasts (CAFs) were identified through multiple bioinformatics analyses. Two novel special cancer-associated fibroblasts were identified as nCAFs and imCAFs. Then, cancer cells in duct cells were identified using the infercnv software. Two ASPC-specific subgroups of cancer cells with squamous cell features were identified. Finally, the identified specific CAFs and cancer cells were mapped to TCGA-PAAD cohort through the cibersoftx software. All of these identified subgroups were calculated to have a significant prognostic value in pancreatic cancer patients. These findings will promote the clinical application of single-cell sequencing data of pancreatic cancer and deepen our understanding of ASPC.

FAM53B promotes pancreatic ductal adenocarcinoma metastasis by regulating macrophage M2 polarization

“…As researchers continue to understand the various biological behaviors of cancer and various cancer treatment strategies[ 31 ], the survival rate for many cancer types and quality of life of patients have been significantly improved[ 31 - 34 ]. However, the prognosis of PDAC is not optimistic due to its early systemic spread, high vascular invasiveness, difficulty in early diagnosis, and resistance to chemotherapy[ 35 - 37 ]. We focused on exploring whether FAM53B knockdown can change the secretion of tumor cytokines, whether the secreted cytokines can affect macrophage polarization, and whether the macrophages with altered polarization status can affect PDAC cell migration[ 38 - 40 ].…”

From Machine Learning to Patient Outcomes: A Comprehensive Review of AI in Pancreatic Cancer

“…By visualizing the reduced dataset, researchers can identify patterns or clusters that may not be immediately apparent in the original data. This can aid in uncovering hidden relationships or identifying novel features relevant to pancreatic cancer [36][37][38].…”

The Role of Genetic, Metabolic, Inflammatory, and Immunologic Mediators in the Progression of Intraductal Papillary Mucinous Neoplasms to Pancreatic Adenocarcinoma

“…Populations of iCAF were identified only in invasive carcinoma, and were absent in non-invasive carcinoma, while myCAF were present even in low-grade dysplastic lesions and increased with progression to high-grade lesions, suggesting that CAFs’ role in inflammation and immune suppression occurs later in the IPMN to PDAC progression timeline [ 51 ]. More subtypes of CAF emerged with regard to PDAC, including mixed fibrogenic and inflammatory types, types without fibrotic or inflammatory features, and antigen-presenting subtypes (apCAF) [ 73 , 74 ]. It is thought that apCAF may act as a decoy receptor to deactivate CD4+ T cells and further contribute to immune suppression [ 74 ].…”