Objective  To explore the molecular mechanisms of green tea polyphenols against pancreatic adenocarcinoma (PAAD) based on network topology, Bulk transcriptomics and spatial transcriptomics.

Methods  Network topology was used to analyze the potential targets of green tea polyphenols against PAAD. The enrichment pathways of target genes and the tumor immune microenvironment were evaluated based on the BEST platform and the GSCA database. The spatial mechanism of target genes was explored through the SpatialTME database.

Results  Green tea polyphenols can intervene in the pathogenesis and progression of PAAD through multiple pathways and targets. The high expression of target genes showed a significant positive correlation with the receptor tyrosine kinase (RTK) signaling pathway. Target genes expression was significantly negatively correlated with the abundance of neutrophils, T helper 2 cells (Th2) and naive CD4-positive T lymphocytes (CD4_naive) (P<0.05), while showing a significant positive correlation with the abundance of mucosal-associated invariant T cells (MAIT), CD4-positive T lymphocytes (CD4_T) and type  1 regulatory T cells (Tr1), etc (P<0.05). The target genes could significantly distinguish responders and non-responders in immunotherapy cohorts receiving anti-programmed cell death protein 1 (PD-1) and anti-PD-1/programmed death-ligand 1 (PD-1/PD-L1) treatments.

Conclusion  This study revealed the tissue localization mechanism of green tea polyphenols' intervention in PAAD. The target genes are expected to serve as tumor markers for PAAD, which is of great significance for its clinical diagnosis and treatment.

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