System Review And Clinical Pathology Evaluation Of PD-L1 As The Potential Biomarker In Breast Cancer

Background Breast cancer occurs in the mammary gland epithelial tissue,with a high degree of heterogeneity,is one of the major cancers in women around the world.The pathogenesis of breast cancer is still not completely clear.According to the degree of invasion it can be divided into invasive cancer and carcinoma in situ.Mostly it occurs as ductal cancer.The main treatment methods are chemotherapy,radiotherapy and surgery.Early diagnosis,treatment and effective prediction of therapeutic effect is the key to improve prognosis and survival rate.Tumor marker is the substance that is abnormally produced or elevated due to the synthesis and release of tumor cells during proliferation,or due to the body's stimulating response to tumors.Tumor marker can be one of the tools for cancer diagnosis and differentiation,guiding clinical therapy and prognosis.The ideal tumor marker is based on high sensitivity and high specificity,which can determine the source of the tumor,as well as being related to the stage and size of the tumor.Moreover,through the detecting of idea tumor marker,the curative effect can be observed,and the recurrence and prognosis tumor can be Inspected.At present,the prevalence of low specificity and sensitivity of tumor marker results in the insufficient in clinical application for early diagnosis,prognosis and treatment decision-making of breast cancer.High expression of programmed death ligand 1(PD-L1)is associated with immune cells and plays a key role in cancer immune evasion,which may be a potential tumor marker.However,for breast cancer patients,the correlation between the expression of PD-L1 and the prognosis and clinicopathological features of breast cancer remains controversial.Objective:To elucidate the correlation of PD-L1 expression between prognosis and clinical features,and to investigate the clinical significance of high expression of PD-L1 inbreast cancer.We used the Meta-analysis of the evidence-based medicine method to comprehensively analyze related literatures.At the same time,the clinical pathological sections of breast cancer tissues and the pathological characteristics of patients were collected.The expression of PD-L1 was detected by immunohistochemistry,and the correlation between the occurrence of high expression of PD-L1 and related clinical features was analyzed.The clinical research can further confirm the significance of high expression of PD-L1 in breast cancer.Methods A comprehensive literature search was performed using the PubMed,Embase and for relevant articles published(up to March 2017).Meta-analysis was conducted by using the STATA14.0 statistical software.The histopathological sections of the breast tumor tissue from a major hospital were collected to conduct a clinical evaluation.The expression of PD-L1 in the tumor tissues was detected by immunohistochemistry,and the corresponding medical records were traced to investigate the correlation between the overexpression of PD-L1 and the clinicopathological features of the patients.Data were analyzed by using SPSS17.0statistical software.Results Finally,18 studies including 5958 patients were included in the pooled analysis.The results of the Meta-analysis section revealed that PD-L1 overexpression in breast cancer patients is negative association with overall survival(HR = 1.16,95%CI:0.78-1.71,P = 0.470).Whereas,in subgroup analyses,PD-L1 overexpression in overall breast cancer group and only TNBC group had HRs of 1.37(95% CI:1.19-2.42,P = 0.004)and 0.58(95%CI: 0.35-0.96,P = 0.035),respectively.Pooled result revealed PD-L1 overexpression negative correlated with DFS.In addition,the correlation between PD-L1 expression and clinic pathological features suggested the pooled ORswere significantly associated with poor tumor cell differentiation(OR =0.48,95%CI: 0.29-0.79,P = 0.004),present of vascular invasion(OR = 0.67,95%CI:0.46-0.99,P = 0.042),positive HER2 status(OR = 1.25,95%CI: 1.03-1.50,P =0.021),and more TILs infiltration(OR = 0.08,95%CI: 0.03-0.24,P <0.001).The results of the clinical evaluation revealed that 46 cases related clinical pathological data were collected,including age,T stage,histological grade,lymph node metastasis,clinical stage,vascular invasion,Ki67 expression level,ER expression level,PR expression level,HER2 expression level,whether triple negative breast cancer or not,and tumor infiltrating lymphocyte expression level.The expression of PD-L1 was observed under microscope after immunohistochemistry.The correlation between high expression of PD-L1 and clinical parameters related to tumor was analyzed after scoring.Chi square test showed that there was a difference between the expression of PD-L1 and different histological grading(grade ? :66.7%vsgrade?-?:33.3%,P=0.019).However,there was no significant difference between the intensity of PD-L1 expression and different age,T stage,histological grade,lymph node metastasis,clinical stage,vascular invasion,Ki67 expression level,ER expression level,PR expression level,HER2 expression level,whether triple negative breast cancer or not(P>0.05).Conclusion 1.Results from systemreviewand Meta-analysis indicated that high expression of PD-L1 was generally associated with poor prognosis of breast cancer,in the contrary,it is associated with better overall survival in triple-negative breast cancer patients.High expression of PD-L1 is associated with poor differentiation,the appearance of vascular invasion,positive HER2 status,and the involvement of more TILs.2.Clinical evaluation supports the result that high expression of PD-L1 is associated with the poor degree of cell differentiation.3.Resultsfrom clinical pathology evaluation basically in accordance with systemreview,which indicate that PD-L1 as the potential biomarker for predicting the prognosis of breast cancer has shown certain clinical significance.