DDR1 in pancreatic adenocarcinoma: unraveling the mechanisms of immune exclusion.

Cheng, Long; Wei, Lina; Chen, Qian; Li, Peirong; Zhang, Dekui

Background: Pancreatic adenocarcinoma (PAAD) is a deadly cancer marked by extensive collagen deposition and limited response to immunotherapy. Discoidin domain receptor1 (DDR1), part of the transmembrane receptor tyrosine kinase family, is linked to inflammation regulation and immune cell infiltration. However, its role in controlling cytokines and chemokines in the microenvironment of PAAD is still unclear. Methods: Initially, RNA sequencing data from TCGA were utilized to investigate the expression of DDR1. Subsequently, the relationship between DDR1 and immune infiltration was examined through Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) analysis, in conjunction with ssGSEA Immunoanalysis. Lastly, the effect of DDR1 on the malignant characteristics of PAAD cells was examined through in vitro experimentation, employing various techniques such as the CCK8 assay, colony formation assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: The research revealed a notable increase in the expression level of DDR1 in PAAD. Subsequent analysis indicated a correlation between the differential expression of DDR1 with chemokines and immune infiltration. Additionally, cellular experiments demonstrated that the downregulation of DDR1 led to enhanced expression of chemokines CCL4, CCL5 and CXCL10. Conclusion: DDR1 is linked to tumor immune infiltration, and the knockout of DDR1 results in the upregulation of chemokines CCL4, CCL5 and CXCL10 in Pan02 PAAD cells.

DISCOIDIN domain receptor 1; PROTEIN-tyrosine kinases; GENE expression; POLYMERASE chain reaction; TREATMENT effectiveness; KINASES

Scandinavian Journal of Gastroenterology, 2025, Vol 60, Issue 1, p81

0036-5521

Academic Journal

10.1080/00365521.2024.2443505