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Although various chemokines have pro-tumorigenic actions in cancers, the effects of CXCL16 remain controversial. The aim of this study was to investigate the molecular characteristics of CXCL16-expressing papillary thyroid cancers (PTCs). CXCL16 expressions were significantly higher in PTCs than benign or normal thyroid tissues. In the TCGA dataset for PTCs, a higher  CXCL16  expression was associated with M2 macrophage- and angiogenesis-related genes and poor prognostic factors including a higher TNM staging and the  BRAF  V600E  mutation. PTCs with a higher expression of 3-gene panel including  CXCL16 ,  AHNAK2 , and  THBS2  showed poor recurrence-free survivals than that of the lower expression group. Next, shCXCL16 was introduced into BHP10-3SCp cells to deplete the endogenous CXCL16, and then, the cells were subcutaneously injected to athymic mice. Tumors from the BHP10-3SCp shCXCL16  exhibited a delayed tumor growth with decreased numbers of ERG +  endothelial cells and F4/80 +  macrophages than those from the BHP10-3SCp control . CXCL16-related genes including  AHNAK2  and  THBS2  were downregulated in the tumors from the BHP10-3SCp shCXCL16  compared with that from the BHP10-3SCp control . In conclusion, a higher CXCL16 expression was associated with macrophage- and angiogenesis-related genes and aggressive phenotypes in PTC. Targeting CXCL16 may be a good therapeutic strategy for advanced thyroid cancer.

CXCL16 positively correlated with M2-macrophage infiltration, enhanced angiogenesis, and poor prognosis in thyroid cancer