Expression And Clinicopathological Significance Of Siglec-15、PD-L1 Protein In Pre-neoadjuvant Triple Negative Breast Cancer

Objective:To detect the expression of Siglec-15 and PD-L1 in pre-neoadjuvant triple negative breast cancer(TNBC),and to explore the relationship between Siglec-15,PD-L1 and the clinicopathological characteristics,the degree of pathological remission,the molecular types of the TNBC,and to analyse the impacts of Siglec-15 and PD-L1 on the survival and prognosis of TNBC.Methods:190 cases of TNBC were collected by preoperative puncture biopsy in the Fujian Medical University Union Hospital affiliated to from January 2008 to December 2020.All of these patients received neoadjuvant chemotherapy chemotherapy(NAC).Collected the informations below: basic clinical;histopathologic slides and paraffin blocks before and after operation;chemotherapy regimens;operations.Immunohistochemical staining was performed to detect the expression of Siglec-15,PD-L1,AR,CD8,FOXC1 and DCLK1 on the biopsy specimens of 190 TNBC,and the control group of 30 cases of breast fibroadenoma and 30 cases of normal breast tissue.According to the results of AR,CD8,FOXC1 and DCLK1,the TNBC were divided into five molecular subtypes: androgen receptor lumen subtype(LAR),immunoregulatory subtype(IM),basal-like immunosuppressive subtype(BLIS),mesenchymal subtype(MES)and unclassified subtype(US).Pathological complete remission(p CR)and residual cancer burden(RCB)were used to evaluate the degree of pathological remission.The collected data were statistically analyzed by SPSS software,Chi-square test was used to compare the distribution differences of Siglec-15,PD-L1 in clinicopathological characteristics and different molecular types.Spearman correlation analysis was used to analyse the correlation of Siglec-15 and PD-L1 in TNBC.Univariate Logistic regression analysis was conducted to analyze the ralationship between Siglec-15,PD-L1,clinicopathological factors and p CR,RCB.Univariate analysis was conducted to screen out statistically significant variables,and further multivariate Logistic regression model analysis was performed.The relationship between Siglec-15,PD-L1 expression,clinicopathological characteristics and prognosis(DFS OS)were analyzed by univariate COX proportional risk regression.Univariate analysis screened out statistically significant variables,and further conducted multivariate COX proportional risk regression model analysis.P < 0.05 was considered as statistically significant difference.Results:(1)190 TNBCs were collected.LAR,IM,BLIS,MES,US were 49,75,54,6 and6 cases respectively.Fifty patients(26.3%)reached p CR.63 cases(33.2%)were RCB grade 0+1.PD-L1 was positive in 70 cases and negative in 120 cases.The expression of Siglec-15 was high in 75 cases and low in 115 cases.(2)The expression of Siglec-15 and PD-L1 in TNBCs were significantly higher than in normal breast tissues and breast fibroadenoma(all P values were<0.05).(3)Siglec-15 and PD-L1 expression were not associated with some clinicopathological features(age,T stage before treatment、N stage before treatment,histological grade of biopsy specimen)(all P values were>0.05).(4)The expression of PD-L1 was negatively correlated with Siglec-15 protein in TNBCs(r=-0.14803,P=0.0415).(5)The expression of Siglec-15 was related to p CR(P<0.05),while PD-L1 was not related to p CR(P>0.05).(6)The expression of Siglec-15 was related to RCB grading(P < 0.05),while PD-L1 was not related to RCB grading(P>0.05).(7)The expression of Siglec-15 was related to molecular typing(P<0.05),while PD-L1 was not related to RCB molecular typing(P>0.05).(8)Univariate survival analysis showed that: The N stage before treatment and RCB grade were correlated with the disease-free survival time(DFS)of TNBC patients after neoadjuvant chemotherapy(all P values were<0.05).Age,T stage before treatment,histological grade of biopsy specimen,expression status of Siglec-15 and PD-L1 had no significant correlation with DFS(all P values were>0.05).RCB grading was correlated with the overall survival time(OS)of TNBC patients after neoadjuvant chemotherapy(P<0.05).Age,T stage before treatment,N stage before treatment,histological grade of biopsy specimen,PD-L1 and Sigrec-15 expression status had no significant correlation with overall survival time(OS)(all P values were>0.05).(9)Multivariate survival analysis showed that RCB was an independent factor of DFS and OS(all P values were<0.05).Conclusion:(1)The expression of Siglec-15 was increased in TNBCs,and was correlated with TNBC molecular typing and RCB grading.Combined with tumor size and lymph node status,the efficacy of neoadjuvant chemotherapy can be predicted and the accuracy of p CR prediction can be improved.(2)The expression of PD-L1 was increased in TNBC.There were no significant correlations with the clinicopathological characteristics of TNBCs,the efficacy of neoadjuvant chemotherapy,recurrence or metastasis and overall survival time.(3)The expression of PD-L1 was negatively correlated with Siglec-15 in TNBC,suggesting that Siglec-15 expression was independent of PD-L1 expression.Siglec-15 may be a complementary target of PD-L1 and provide reference for future clinical immunotherapy and research.