Clinicopathological Study Of Immune Related Molecules In Primary Breast Cancer And Bone Metastases

Objective:In order to explore the pathogenesis of the disease,the different expressions of Siglec-15,PD-1,PD-L1,PD-L1 and PD-L2 in primary bone metastasis and bone metastasis of breast cancer patients were evaluated by immunohistochemistry,and the relationship between the differential expression and clinicopathological parameters was analyzed,so as to evaluate whether targeted therapy can improve the survival rate of breast cancer patients and provide some reference for targeted therapy of breast cancer patients test.Methods:From October 2009 to August 2020,94 patients with breast cancer and bone metastasis were selected as tumor biopsy or surgical resection.Each piece needs at least 100 tumor cells,stained with related antibodies,including 60 cases of primary breast cancer,50 cases of bone metastases of breast cancer,including 16 cases.The clinicopathological data of primary breast cancer and bone metastases were summarized and sorted in detail.Siglec-15,PD-1,PD-L1,PD-L1 and PD-L2 were detected by 1:200 IHC staining.We analyzed the relationship between the expression of four immune checkpoints and clinicopathological,and we also analyzed the correlation between the expression of four immune checkpoints and PFS and OS in breast cancer patients with bone metastasis.Spss22.0 chi square test and nonparametric test were used.Analyze the statistical differences between the data.We used the percentages for various count data.For PFS and OS analysis,we also used the Kaplan Meier method to analyze the survival time,and log rank test was performed;K-M univariate analysis and Cox proportional hazard regression model were used,we also used 95% confidence interval to analyse the influence of immune checkpoint expressions on survival time,and the length of univariate analysis was analyzed.In all the results,P < 0.05 was considered statistically different.Results:1.In all primary lesions(n = 60),Siglec-15 was positive in 23(38.3%),PD-L1 in 20(33.3%),PD-1 and PD-L2 in 19(31.7%)and 17(28.3%).Among all bone metastases(n =50),22(44.0%)were Siglec-15 positive,17(34.0%)were PD-1 and PD-L1 positive,16(32.0%)were PD-L2 positive,and only 15(30.0%)were PD-L2 positive.2.Siglec-15 was associated with the molecular type(P = 0.002)and pathological type(P = 0.033)of breast cancer and the expression of PR(P = 0.002),ER(P = 0.029)and HER-2(P = 0.000).The expression of PD-1 was correlated with molecular type(P =0.001),lymph node metastasis(0.012),PR(P = 0.023),ER(P = 0.000)and HER-2(P =0.041).The expression of PD-L1 was only related to molecular type(P = 0.001)and ER(P = 0.012),but not PR(P = 0.056)and HER-2(P = 0.208).The expression of PD-L2 was correlated with molecular type(P = 0.000),pathological type(P = 0.043),lymph node metastasis(P = 0.000),PR(P = 0.039)and HER-2(P,0.002),but not with ER(P = 0.052).The expressions of siglec-15,PD-1,PD-L1 and PD-L2 in breast cancer patients were significantly correlated with the molecular types of breast cancer patients.3.In matched patients,the consistent rate of Siglec-15 expression was 31.3%(5 / 16,kappa = 0.613,P = 0.013).There was significant difference in the expression of Siglec-15 between primary lesions and bone metastases(= 0.333,P = 0.013).At the same time,the consistency rate of PD-1 expression was only 12.5%(2 / 16,kappa = 0.034,P =0.889).There was no significant difference between primary lesions and bone metastases(= 0.143,P = 0.889).The concordance rate of PD-L1 expression was only 18.8%(3 /16,kappa = 0.310,P = 0.210).There was no significant difference between primary tumor and bone metastasis(= 0.200,P = 0.210).For PD-L2,the coincidence rate was 25.0%(4 / 16,kappa = 0.846,P = 0.001).There was a significant difference between primary lesions and bone metastases(= 1.000,P = 0.001).4.In 50 cases of breast cancer with bone metastasis(n = 50),the median PFS and OS were 18.60 months and 23.40 months,respectively.The expression of Siglec-15 in bone metastasis was correlated with OS(HR = 1.82,95% CI: 0.83-4.00,P = 0.04),but not with PFS.However,PFS and OS of the breast cancer patients were not significantly correlated with the expressions of PD-1 and PD-L1.For PD-L2 positive patients,the median PFS and OS were 21.75 months and 22.75 months,respectively.The positive expression of PD-L2 was closely related to OS(HR = 2.32,95% confidence interval: 0.86-6.22,P =0.03).It can be seen that the expression of signal Siglec-15 and PD-L2 in bone metastasis has a certain correlation with OS.Conclusion:1.Siglec-15,PD-1,PD-L1 and PD-L2 were expressed in primary breast cancer and bone metastasis.The expression rate of Siglec-15 was the highest.Siglec-15,PD-1 and PD-L2 were higher in bone metastases,and PD-L1 was higher in primary breast cancer.2.The expression of Siglec-15,PD-1,PD-L1 and PD-L2 were significantly different in different molecular types of breast cancer.The expression of Siglec-15 and PD-L2 was the highest in three cases of negative breast cancer,while the expression of PD-1 and PD-L1 was the highest in Luminal type B.3.In matched patients,Siglec-15 and PD-L2 were significantly different in primary lesions and bone metastases,while PD-1 and PD-L1 were not significantly different,indicating that Siglec-15 and PD-L2 may promote bone metastasis of advanced breast cancer.4.The expressions of Siglec-15 and PD-L2 in bone metastases were negatively correlated with OS,but not with PFS.These results indicate that Siglec-15 and PD-L2 are of great significance in predicting the survival of breast cancer patients,and can be trusted targets for the therapy of bone metastasis of breast cancer.