Identification of therapeutic targets and prognostic biomarkers in the CCL family in the SKCM microenvironment

Abstract Background: Skin cutaneous melanoma (SKCM) is one of the most common malignancies and is one of the most aggressive and dangerous types of skin cancer. CC chemokines in the tumor microenvironment can promote intercellular communication and modulate the transport of immune cells, thus exerting anti-tumor immune effects. The expression of CC chemokines in SKCM, their prognostic value and their relationship with immune cell infiltration are unclear.Methods: Studies were performed using GEPIA, UALCAN, cBioPortal, STRING, GeneMANIA, Omicshare, David 6.8, Metascape, TRRUST, LinkedOmics and Timer.Results: In SKCM we found that CCL3, CCL4, CCL5, CCL8, CCL18 were highly expressed in tumor tissue, while a proportion of CC chemokines CCL14, CCL21, CCL22, CCL23, CCL27 were found to be expressed at low levels. The expression of CCL4, CCL5, CCL8, CCL23, CCL27 was closely related to the pathological stage of SKCM. High expression of CCL3, CCL4, CCL5, CCL8, CCL15, CCL21, CCL22, CCL23 tended to correlate with a good prognosis for patients with SKCM. The functions of the differentially expressed CC chemokines are mainly Chemokine signaling pathway, Cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, Cytosolic DNA-sensing pathway. RELA and NFKB1 are key transcription factors for CC chemokines. We identified a number of kinases associated with differentially expressed CCL. Among them CASP7, SERPINE1, LCK and PRKAA1 are strongly correlated. We also found that expression of CC chemokines was significantly associated with infiltration of multiple immune cells.Conclusion: Our findings may provide new insights into the selection of therapeutic targets and prognostic biomarkers for patients with SKCM.