A Comprehensive Transcriptional Signature in Pancreatic Ductal Adenocarcinoma Reveals New Insights into the Immune and Desmoplastic Microenvironments

Abstract

Pancreatic ductal adenocarcinoma (PDAC) prognoses and treatment responses remain devastatingly poor due partly to the highly heterogeneous, aggressive, and immunosuppressive nature of this tumor type. The intricate relationship between the stroma, inflammation, and immunity remains vaguely understood in the PDAC microenvironment. Here, we performed a meta-analysis of stroma-, and immune-related gene expression in the PDAC microenvironment to improve disease prognosis and therapeutic development. We selected 21 PDAC studies from the Gene Expression Omnibus and ArrayExpress databases, including 922 samples (320 controls and 602 cases). Differential gene enrichment analysis identified 1153 significant dysregulated genes in PDAC patients that contribute to a desmoplastic stroma and an immunosuppressive environment (the hallmarks of PDAC tumors). The results highlighted two gene signatures related to the immune and stromal environments that cluster PDAC patients into high- and low-risk groups, impacting patients’ stratification and therapeutic decision making. Moreover, HCP5, SLFN13, IRF9, IFIT2, and IFI35 immune genes are related to the prognosis of PDAC patients for the first time.

Pancreatic Cancer Health Disparity: Pharmacologic Anthropology

“…Variations in genes involved in drug metabolism and response pathways can contribute to disparities in treatment outcomes and side effects among different populations. The tumor microenvironment, including the immune system and stromal components, influences PCa progression and treatment response [88,90,98,106].…”

Targeted Nanoparticle-Based Diagnostic and Treatment Options for Pancreatic Cancer

“…The intricate nature of PDAC is marked by genetic heterogeneity, increased interstitial fluid pressure, and dense tumor stroma, creating a complex microenvironment [6][7][8]. This significantly enhances the metastatic potential and drug resistance, thereby obstructing the effective delivery of therapeutic agents by conventional chemotherapy treatment approaches.…”

Nanotechnology-Based Strategy for Enhancing Therapeutic Efficacy in Pancreatic Cancer: Receptor-Targeted Drug Delivery by Somatostatin Analog

“…PDAC's complexity is underscored by its genetic diversity, elevated interstitial fluid pressure, and thick tumor stroma, which contribute to a challenging microenvironment. These factors notably amplify its tendency to metastasize and resist drugs, making it difficult for conventional chemotherapy treatments to deliver therapeutic agents effectively [3][4][5]. Nanotechnology has risen as a critical field in tackling the complexities of diverse cancer types through innovative therapeutic and diagnostic approaches [6][7][8][9].…”