A Comprehensive Transcriptional Signature in Pancreatic Ductal Adenocarcinoma Reveals New Insights into the Immune and Desmoplastic Microenvironments.
Irene Pérez-DíezZoraida AndreuMarta R HidalgoCarla Perpiñá-ClériguesLucía FantínAntonio Fernandez-SerraMaría de la Iglesia-VayáJose Antonio Lopez-GuerreroFrancisco García-GarcíaPublished in: Cancers (2023)
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.
Keyphrases
- gene expression
- end stage renal disease
- newly diagnosed
- ejection fraction
- chronic kidney disease
- oxidative stress
- peritoneal dialysis
- dna methylation
- decision making
- bone marrow
- machine learning
- transcription factor
- dendritic cells
- smoking cessation
- deep learning
- big data
- combination therapy
- artificial intelligence
- replacement therapy