Comprehensive assessment of PD-L1 and PD-L2 dysregulation in gastrointestinal cancers.

and are ligands of . Their overexpression has been reported in different cancers. However, the underlying mechanism of and dysregulation and their related signaling pathways are still unclear in gastrointestinal cancers. The expression of and were studied in The Cancer Genome Atlas and Genotype-Tissue Expression databases. The gene and protein alteration of and were analyzed in cBioportal. The direct transcription factor regulating / was determined with ChIP-seq data. The association of expression with clinicopathological parameters, survival, immune infiltration and tumor mutation burden were investigated with data from The Cancer Genome Atlas. Potential targets and pathways of and were determined by protein enrichment, WebGestalt and gene ontology. Comprehensive analysis revealed that and were significantly upregulated in most types of gastrointestinal cancers and their expressions were positively correlated. was a key transcription factor regulating the expression of . Higher or expression was significantly associated with poor overall survival, higher tumor mutation burden and more immune and stromal cell populations. Finally, HIF-1, ERBB and mTOR signaling pathways were most significantly affected by and dysregulation. Altogether, this study provided comprehensive analysis of the dysregulation of and , its underlying mechanism and downstream pathways, which add to the knowledge of manipulating for cancer immunotherapy.