Relationship Between Expression Of Chemokines And Its Receptor MRNA And Pathological Features In Local Lymph Node Tissues Of Melanoma

Objective : Some chemokines/receptors have previously been reported to drive immune cells in tumors or to directly involve in encouraging or inhibiting the development of tumors,whereas a limited number of research has looked into chemokine/receptor expressions in metastasis regional lymph node tissues with melanoma.This study investigated the relationship between the expression of chemokines/receptor mRNA and clinicopathology in the metastasis regional lymph node tissues of SKCM(Skin cutaneous melanoma,SKCM)in The Cancer Genome Atlas(TCGA).Furthermore,this study explored the relationship between chemokine/receptor in regional lymph node tissues in SKCM area and the composition of tumor immune cell.Methods: We screened 222 cases of SKCM from regional lymph node tissue from TCGA-SKCM RNASeqv2.We first used the CIBERSORT algorithm to calculate all RNASeqv2 data,obtaining 22 composite scores of immune cells.Second,we extracted 60 kinds of chemokine/receptor mRNAs from all RNASeqv2 to analyze the relationship between chemokine/receptor gene mRNA and clinical pathology of SKCM(including gender,age,TMN stage,and AJCC grade),as well as the relationship between 22 kinds of composite scores of immune cells and chemokines/receptors.Univariate COX regression was used to assess the survival risk of chemokines/receptors.LASSO regression was used for chemokines/receptors with significant survival differences to obtain a scaled LASSO score.Multivariate COX regression analysis was then conducted using the LASSO score.Results: There was no significant difference between chemokines/receptors in the SKCM regional lymph node tissues in different period of TMN,as well as between chemokines/receptors in different clinicopathological levels.There were significant differences in the survival risk of 33 kinds of chemokine/receptors in SKCM regional lymph node tissues between the high expression group and low expression group.Among them,32 kinds of chemokine/receptor had higher survival prognosis in the high expression group than in the low expression group,whereas one kind(CXCL17)had lower survival prognosis in the high expression group than in the low expression group.And some chemokines/receptors are associated with the composite scores of the immune cell in the tumor microenvironment.CXCL9,-10,-11,-13,CXCR3,-6,CCL2,-4,-5,-7,-8,-25,CCR1,-2,-5,XCL1,-2 were positively correlated with CD8+ T cells,and M1 macrophages,and were negatively correlated with M0 macrophages.CCR,-4,-6,-7,-8,-9,CCL13,-22,-23,and XCR1 were positively correlated with memory B cells and navie T cells,and negatively correlated with M0 macrophages and resting mast cells.After LASSO rating of 32 kinds of chemokines/receptors,4 kinds of chemokines/receptors(CCL2,8,CXCL10,16)were used to build a LASSO scoring model.The results showed that 4 kinds of chemokines/receptors were negatively correlated with LASSO scores,and the scaled LASSO score was an independent prognostic factor in multivariate COX risk analysis(HR: 0.39,95% CI: 0.24-0.65,p < 0.001).The results from multivariate analysis also showed it was an independent prognostic factor,when age(HR: 1.68,95% CI: 1.06-2.67,P=0.027<0.05),T stage(HR: 0.40,95% CI: 0.22-0.73,P=0.007<0.01),N stage(HR: 1.9,95% CI: 0.22-0.73,P=0.385<0.05),and CXCL17(HR: 0.40,95% CI: 0.22-0.73,P=0.003<0.05)were included.In addition,the limited number of pathological cases in M1 stage may result in no statistically significant difference(p = 0.471).Conclusion: In SKCM regional lymph node tissues,the high expression of 32 kinds of chemokines/receptors,namely CCL2,4-5,7-8,13,22-25,CCR1-9,CXCL9-13,16,CXCR3,5,6,XCL1-2 and XCR1,may suggest that patients have a good prognosis.High expression of CXCL17 may be considered as an indicator for poor prognosis.In addition,the expression of chemokine/receptor in regional lymph node tissue is not related to T,N stage and AJCC classification of the patients.Based on the LASSO scores of 32 chemokines/receptors,CXCL17,T,and N stages were patient-independent prognostic markers.In the SKCM regional lymph node tissue,CXCL9,-10,-11,-13,CXCR3,-6,CCL2,-4,-5,-7,-8,-25,CCR1,-2,-5,XCL1,-2 were positively correlated with CD8+ T cells,and M1 macrophages,and were negatively correlated with M0 macrophages.CCR,-4,-6,-7,-8,-9,CCL13,-22,-23,and XCR1 were positively correlated with memory B cells and navie T cells,and negatively correlated with M0 macrophages and resting mast cells.Moreover,CD8 T cells,M1 macrophages,B cells,and navie T cells are associated with good prognosis,suggesting that chemokines/receptors may affect the prognosis of patients by guiding immune cells into the tumor microenvironment to kill tumor cells.