Expression And Significance Of HMGB1 And PD-L1 In Nonspecific Invasive Breast Carcinoma

Background:Breast cancer has become the leading cause of morbidity and mortality of malignant tumors in many countries.China has a large population,and the number of patients and deaths is the highest in the world.There are many histological types of breast cancer,the most common of which is non-specific invasive breast carcinoma.The development of programmed cell death ligand 1(PD-L1)has made great progress in the past decade,and many drugs have been approved,but the use of PD-L1 in breast cancer is still in the research and initial stage.Many molecular pathways and disease-related effects of high mobility group box 1(HMGB1)have been found,but there are few studies on HMGB1 and breast cancer,its targeted treatment is still in the basic experimental stage.HMGB1 and PD-L1 play an important role in tumor microenvironment,helping tumor cells escape from immunosuppression,and they have certain relationship.The co-expression of HMGB1 and PD-L1 in non-specific invasive breast carcinoma has not been reported yet.This study will carry out innovative research and exploration in this area.Purpose:To investigate the expression of high mobility group box 1(HMGB1)and programmed cell death ligand 1(PD-L1)in non-specific invasive breast carcinoma and their relationship with clinicopathological parameters,and to evaluate the correlation between HMGB1 and PD-L1,and its significance in clinical prognosis of non-specific invasive breast carcinoma.Methods:1.We extracted and analyzed the expression of HMGB1 and CD274(PD-L1)genes in non-specific invasive breast carcinoma from TCGA database by bioinformatics method.2.We collected the pathological section,wax block and clinical data of 257 cases of non-specific invasive breast carcinoma.The expression of HMGB1 and PD-L1 in non-specific invasive breast carcinoma and normal breast tissue was detected by immunohistochemical method,and analyzed the relationship between each other and the clinicopathological features,to evaluate the prognostic value.Results:1.TCGA data mining explored the expression of HMGB1 and CD274(PD-L1)in non-specific invasive breast carcinoma at the gene level,find out there was a significant positive correlation between each other(P<0.05).Further analysis showed that there was significant difference in expression between triple negative breast cancer and other molecular types(P<0.05),and there was a significant positive correlation between each other(P<0.05).The GO enrichment analysis and KEGG enrichment analysis of HMGB1 and CD274(PD-L1)showed that there was a significant correlation between them in a variety of tumor microenvironment related functions such as cell differentiation and immune response,and molecular pathways such as T / B cell receptor pathway and a variety of tumors(P<0.05).The survival analysis showed that both HMGB1 and CD274(PD-L1)were negatively correlated with the recurrence free survival rate(P<0.05).2.The expression of HMGB1 in tumor cells of non-special invasive breast carcinoma(207/257,80.5%)was significantly higher than that in normal breast cells(118/257,45.9%)(P<0.05).The positive rate of PD-L1 was 37.7%(97/257).3.The high expression of HMGB1 was related to tumor size,histological grade,axillary lymph node metastasis and TNM stage(P<0.05).The expression of PD-L1 was related to histological grade,axillary lymph node metastasis,TNM stage,estrogens receptor,progesterone receptor,HER2 and molecular type(P<0.05).4.HMGB1 high expression was significantly correlated with PD-L1 positive in the high grade of non-special invasive breast carcinoma(P<0.05),and there was a significant positive correlation between HMGB1 and PD-L1 in triple negative breast cancer(P<0.05).5.In terms of prognosis,HMGB1 high expression and PD-L1 positive were negatively correlated with the five years recurrence free survival rate of patients with non-specific invasive breast carcinoma(P<0.05).Conclusions:1.HMGB1 and PD-L1 were found to be significantly positively associated with each other in non-specific invasive breast carcinoma at both gene and protein levels.2.HMGB1 and PD-L1 were found to be significantly negative correlated with the recurrence free survival rate of non-specific invasive breast carcinoma patients at both gene and protein levels.