| Objective:To further understand the expression of Dkk1 in prostate cancer and its significance during bone metastasis and to clarify the role of Dkk1 in the progression of prostate cancer,and to provide a new direction for the diagnosis and treatment of prostate cancer.Methods:By constructing prostate cancer cell lines,To compare the expression of Dkk1 protein in prostate cancer with different metastatic potential.Also the difference of Dkk1 expression between normal prostate tissue and prostate cancer tissue was further compared by tissue microarray and paraffin section.Finally,the use of public database data,through SPSS and R and other software for clinical characteristics and bioinformatics analysis,to explore the role of Dkk1 in prostate cancer.Results:Through the detection of Western Blot in each prostate cell line,we found that Dkk1 was highly expressed in PC3 cell line derived from bone metastasis(p=0.0002,<0.001),and in further tissue section verification,we also found that the expression of Dkk1 in prostate cancer tissue was higher than that in normal prostate tissue(p=0.007,<0.05).The results of clinical characteristic analysis and bioinformatics analysis of public database showed that Dkk1 showed a close relationship with metastasis in both Taylor database and TCGA database.After bioinformatics analysis of Dkk1 transcriptome data and tumor microenvironment-related immune cells and immune targets,it was found that.The expression of Dkk1 in prostate cancer was closely related to the composition of immune microenvironment in tumor microenvironment(p < 0.001).After analyzing the correlation between the expression of Dkk1 and the key immune checkpoint(Check point),we found that there was a close relationship between Dkk1 and CTCN1,VSIR,TNFSF9,LGALS9,HAVCR2,CD86,CD40,CD200 in the immune checkpoint(P < 0.001).After further analysis of the targets in the immune microenvironment,it was found that the high expression of Dkk1 was related to the immune pathways of many kinds of immune cells and immunomodulatory cells,including T lymphocytes,B lymphocytes,neutrophils,macrophages and so on(p < 0.001).Conclusions:The high expression of Dkk1 in tumor tissues,especially in tumor cells derived from bone metastasis,suggests that it may be a potential molecular marker for early bone metastasis of prostate cancer,and that the high expression of Dkk1 is closely related to various immune checkpoints and immune cell pathways in the immune microenvironment of prostate tumor.It is suggested that Dkk1 may promote tumor bone metastasis by inhibiting the monitoring and killing effect of immune cells on tumor by acting on immune checkpoints in the immune microenvironment of prostate cancer. |
PDF Full Text Request