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Potential roles of PBRM1 on immune infiltration in cholangiocarcinoma.

BACKGROUND
Cholangiocarcinoma (CHOL) is one of the most fatal malignancies worldwide. PBRM1 is a tumor suppressor gene in diverse cancers. It regulates cell cycle, genomic stability, centromeric cohesion, and apoptosis. However, its relevance to remodel tumor cell immune response of PBRM1 in CHOL remains unclear.


METHODS
PBRM1 mutation and expression of CHOL patients were analyzed by the TCGA database using R packages and cBioPortal site. The correlation between PBRM1 and tumor cell immune inﬁltrates among CHOL patients was investigated by TIMER2.0. Correlation analysis between PBRM1 and gene markers of tumor-inﬁltrating immune cells in CHOL was analyzed by GEPIA. Pathway enrichment analysis and protein-protein interaction network of PBRM1 mutation and expression was investigated using STRING and Cytoscape.


RESULTS
Among CHOL patients, PBRM1 has a high mutation probability and significant differential expression. Mutations and differential expression of PBRM1 both have a significant effect on the infiltration of cancer associated fibroblasts (CAF) in CHOL patients. PBRM1 was highly correlated with MMP2 and FAK, which were reported as key regulators of CAF. Through protein-protein interaction network with hub gene analysis, we discovered that NCAM1 could play key roles in the potential mechanism of how PBRM1 affects immune infiltration and progress of CHOL.


CONCLUSION
PBRM1 may play an important role in immune cell infiltration, matrix formation, and tumor invasion of CHOL, by regulating the function and infiltrating of tumor stromal cells including cancer-associated fibroblasts through NCAM1. Therefore, PBRM1 might be a new therapeutic target in CHOL.