Expression And Correlation Of Programmed Death Ligand-1 And P53 In Triple-negative Breast Cancer

BackgroundTriple-negative breast cancer(TNBC)is a subtype of breast cancer with the strongest immunogenicity,but the objective response rate(ORR)to immunotherapy is different.The most common tumor suppressor gene p53,can communicate with cytotoxic t-lymphocyte(CTL)through proteins such as inhibitory immune checkpoint ligands(such as programmed death ligand-1,PD-L1)and control response of CTL to tumor cells,finally facilitate CTL-induced tumor cell death.PurposeTo detect protein levels of PD-L1 and p53 in both TNBC and non-triple-negative breast cancer(non-TNBC).To analyze correlations between PD-L1 and p53 in mRNA levels and protein levels in TNBC.To analyze clinical and prognosis significances of protein levels of PD-L1 and p53 in TNBC.Materials and methodsA total of 164 breast cancer specimens retained by the Department of Pathology of Chongqing Medical University were selected,including 132 cases of TNBC and 32 cases of non-TNBC.The paraffin-embedded tumor tissues were prepared into 4-um thick sections.Immunohistochemistry(IHC)was used to detect protein levels of PD-L1 and p53,and differences of expressions were analyzed.Clinicopathological information and survival status of TNBC were collected through electronic medical record(EMR)and telephone follow-ups.The relationships between protein levels of PD-L1,p53 in TNBC and clinicopathological factors were analyzed by Chi-square test.Correlations between PD-L1 and p53 in TNBC were analyzed by Spearman rank correlation analysis both in protein levels and mRNA levels.mRNA levels of PD-L1 and p53 were obtained by Gene Expression Omnibus(GEO,GSE76275).Relationships between PD-L1,p53 and survival status were analyzed by Kaplan-Meier curve.The expressions of PD-L1 in tumor cells(TCs)and tumor-infiltrating immune cells(TICs)were analyzed respectively.ResultsIn TNBC,positive rates of PD-L1 on TCs and TICs were 37.1%(49/132),40.2%(53/132),which were higher than non-TNBC(15.6%,5/32,28.1%,9/32),but the difference was only statistically significant in the TCs group(p<0.05).Positive rate of p53 in TNBC was 68.2%(90/132),which was statistically significant higher than non-TNBC(46.9%,15/32,p<0.05).In TNBC,the expression of PD-L1 in TCs was significantly correlated with tumor histological grade,tumor size,lymph node metastasis status and Ki-67 index(p<0.05).The expression of PD-L1 in TICs was only correlated with tumor histological grade(p<0.05).The expression of p53 was significantly correlated with tumor histological grade,tumor size and Ki-67 index(p<0.05).Correlation analysis in TNBC showed that protein levels of PD-L1 in TCs,PD-L1 in TICs and p53 were positively correlated in pairwise.However,a negative correlation was found in mRNA levels of PD-L1 and p53 in TNBC.Survival analysis showed that negative groups of PD-L1 and p53 had better overall survival(OS)and progression-free survival(PFS)than positive groups,but marginal statistical significances were only found in the OS of TCs PD-L1 group,OS of TICs PD-L1 group and PFS of TICs PD-L1 group(0.05≤p<0.1).ConclusionCorrelation between PD-L1 and p53 was found in TNBC and the expression of PD-L1 and p53 were closely correlated with prognostic factors and survival outcomes.The positive correlation in protein levels indicated a synergistic effect between PD-L1 and mutated type p53(mtp53)in the process of tumor progression.These findings would lay foundation for further study on the relationship of PD-L1 and p53 and the combination of mtp53 inhibitors and anti-PD-1/PD-L1 in TNBC.