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

Autores de CIPF

• Zoraida Andreu Martínez

  Autor

• Marta Rosa Hidalgo García

  Autor

• María De La Iglesia Vayá

  Autor

• José Antonio López Guerrero

  Autor

• 

  Francisco García García

  Autor

Participantes ajenos a CIPF

• Pérez-Díez I
• Perpiñá-Clérigues C
• Fantín L
• Fernandez-Serra A

Grupos de Investigación

• Unidad de Bioinformática y Bioestadística

  

  Jefe/a de Grupo

  Francisco García García

• Unidad Mixta CIPF-FISABIO de Imagen Biomédica

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.

Keywords

• biomarkers, desmoplasia, heterogeneity cancer, immune system, meta-analysis, molecular profile, pancreatic ductal adenocarcinoma, prognosis, transcriptomics