CXCL5 expression is associated with active signals of macrophages in the microenvironment of papillary thyroid carcinoma

Background: C-X-C motif chemokine ligand 5 (CXCL5) is a chemokine molecule that is secreted by immune cells in attracting granulocytes. Studies showed that CXCL5 was related to the progression of papillary thyroid carcinoma (PTC) tumor cells. However, the in vivo effects of CXCL5 on PTC tumor cells and their microenvironment have not been elucidated. The present study aimed to investigate the biological effects of CXCL5 on tumor cells, microenvironment, and clinical progression of PTC. Materials and methods: The PTC patients from The Human Cancer Genome Atlas (TCGA) - thyroid carcinoma (THCA) were retrieved. There were a total of 500 patients who met the criteria of our study. Differential expression (DEA) and pathway analyses were used to explore the biological effects of CXCL5 gene expression. Results: In DEA, we found that CXCL5 was mostly associated with PBPP, SLC11A1, and MRC1 (adjusted p<0.001). Samples with CXCL5 FPKM >= 1 were related to a different immune profile (p<0.001). In pathway analyses, samples with higher CXCL5 expression possessed higher activities of RAS-RAF, NF-kB, PRC2, IL2, IL5, and Wnt pathways (adjusted p<0.001). In microenvironment analysis, CXCL5 was highly correlated with the activity of macrophage (Rho=0.76; adjusted p<0.001). Clinically, high level of CXCL5 expression was an indicator of tumor stages (p<0.001), nodal metastasis (AUC=0.68), and prognosis (p=0.001). Conclusion: CXCL5 was a significant biomarker of PTC. CXCL5 was highly associated with tumor immunology and microenvironment. Samples with higher CXCL5 expression had more advanced disease status and worse prognosis. CXCL5 target therapy is potentially helpful in advanced PTC.