| Objective: Small cell lung cancer（SCLC）is highly malignant and invasive wide range of movement.Conventional chemotherapy regiments of etoposide com-bined with carboplatin or cisplatin have an effective rate of about 60-65%,with most cases relapsing and showing resistance.In recent years,immune Checkpoint inhibitors have made significant progress in the treatment of SCLC,Nivolumab and Pembrolizumab have been approved by the Food and Drug Administration（FDA）forsecond-line and beyond treatment in patients with widespread SCLC.The study found that there seemed to be better response rate and survival rate.In extensive SCLC with a positive rate of PD-L1 in tumor cells > 1%,suggesting that PD-L1 can predict the immunotherapy effect and survival rate in this SCLC sub-group.However,some studies have found poor correlation Between PD-L1 expression and response in tumor cells in some SCLC.These results raise the question: PD-L1 expression different in different types of SCLC,and what is the prognostic significance of its expression? A recent study found that low-dose antidelta-li-ke Ligand3（DLL3）targeted therapy combined with PD1/PD-1inhibitors can enhance theimmunotherapy effect in mouse SCLC models,and studies have found that DLL3 protein expression is positively correlated with PD-L1.In addition,studies haveshown that PD-L1 expression is more common in central type SCLC with positive thyroid transcription factor 1（TTF-1）,suggesting that TTF-1 expression and tumor location can predict the expression status of PD-L1 in SCLC.In addition,the expression of TTF-1 protein was also positively Correlated with the expression of DLL3.On the other hand,the prognostic relationship between PD-L1 and TTF-1 and SCLC is controversial.Therefore,this project aims to analyze the expression of PD-L1,TTF-1 and DLL3 proteins in SCLC,their correlation with each other,and the impact of the expression of the three proteins on the prognosis of SCLC.Methods: Immunohistochemistry（IHC）En Vision two-step method was used to detect PD-L1,TTF-1 and DLL3 expressions in paraffinembedded tissues of116 cases of small cell lung cancer.Fisher’s exact test or Chi-square test were used for comparison of categorical variables,and Spearman’s test was used for correlation analysis.Univariate analysis was performed by log-rank test,survival prognosis was analyzed by Kaplan-Meier method.Multivariate analysis was Performed using Cox proportional risk regression model.Results: 1.PD-L1 protein was expressed in the membrane and cytoplasm of SCLC tumor cells,and the positive rate was 14.7%（17/116）.TTF-1 protein was expressed in the nucleus of SCLC tumor cells with a positive rate of 80.2%（93/116）.DLL3 protein was expressed in the cytoplasm of SCLC tumor cells,and its high expression rate was 76.7%（89/116）.The expression of TTF-1 protein was positively correlated with DLL3,while there was no correlation between PD-L1 protein,DLL3 and TTF-1.2.TTF-1 expression was positively correlated with the expression of CD56,Syn,Cg A,DLL3 and the elevation of gastrinreleasing peptide precursor（Pro GRP）.DLL3 expression was positively correlated with Syn expression and Pro GRP elevation.3.Univariate analysis results: No chemotherapy（P < 0.001）,Pro GRP elevation（P=0.006）,TTF-1 and DLL3 protein expression（P=0.013,0.002）were associated with shorter Overall Survival（OS）.The OS of DLL3 low /TTF-1-subgroup was longer than that of other subgroups（P < 0.001）.4.Multivariate analysis results: Pro GRP level,chemotherapy status,combined TTF-1 and DLL3 protein detection were independent risk factors for SCLC OS.Conclusions: Combined antibody DLL3 and TTF-1 detection is an independent prognostic measure with higher prognostic value than single antibody detectio n,and TTF-1 expression can be used as a predictor of anti-DLL3-targeted therapy in SCLC patients. |
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