Expression Of PD-1/PD-L1 In Esophageal Squamous Cell Carcinoma And Its Prognostic Value

Background:Esophageal cancer is the eighth most common cancer in the world and the sixth leading cause of cancer-related deaths.Its incidence has increased year by year and has seriously threatened human health.According to histological classification,esophageal squamous cell carcinoma(ESCC)and adenocarcinoma are the two main pathological types of esophageal cancer,of which the former accounted for 90%of esophageal cancer cases in China.Although medical technology is constantly improving,the overall 5-year survival rate is still unsatisfactory due to its malignant characteristics and the fact that most patients are at a later stage of diagnosis.Even if the patient undergoes a curative surgical resection,local recurrence or distant metastasis often occurs.The latest breakthroughs in the study of immunological checkpoints and their inhibitors have contributed to the advent of a new era of cancer immunotherapy,driving the transformation of cancer treatment modalities.Programmed cell death-1(PD-1)and programmed cell death-ligand 1(PD-L1)are a pair of inhibitory co-stimulatory molecules whose expression is a key regulator of T lymphocyte-mediated immune responses.PD-1 binds to PD-L1 and transmits an inhibitory signal to create an immunosuppressive tumor microenvironment,helping the tumor to escape immune killing and promote tumor progression.A number of studies have confirmed that PD-1/PD-L1 plays a crucial role in tumorigenesis and development,and affects the prognosis of patients.PD-1/PD-L1 produces immunosuppressive effects in various types of solid tumors,allowing tumors to avoid T lymphocyte-mediated cytolysis.At present,PD-1/PD-L1 has become a research hotspot as a target for tumor immunotherapy,but it has been reported relatively less in esophageal cancer.Committed to this,this study explored the expression of PD-1/PD-L1 in esophageal squamous cell carcinoma and its prognostic value.Purpose:To investigate the expression of PD-1 and PD-L1 in ESCC,and study its relationship with various clinicopathological factors and prognostic value.Methods:The expression of PD-1/PD-L1 in 40 cases of ESCC was detected by immunohistochemistry.Statistical software SPSS 19.0 was used for statistical analysis.The?~2 test(or Fisher's exact test,if appropriate)was used to analyze the relationship between its expression and clinicopathological factors and prognosis.Kaplan-Meier and Log-rank methods were used for survival analysis.Cox regression model was used for prognostic factors analysis.The statistically significant difference was set P<0.05.Results:In this study,5%and 10%were used as positive expression thresholds,and the corresponding PD-1 positive expression rates were 62.5%(25/40)and 55%(22/40),respectively.The positive expression rate of PD-L1 was 30%(12/40)and 25%(10/40).When5%was used as the expression threshold,the expression of PD-1 and PD-L1 was not related to gender,age,degree of differentiation,length of lesion,smoking,alcohol consumption,lymph node metastasis,T stage and tumor location;10%was used as the expression threshold,the expression of PD-L1 was associated with tumor T stage.The positive rate of PD-L1 was10%(2/20)in stage<T3 stage,and 40%(8/20)in?T3 stage,P=0.028.The tumor markers included in this study were CEA,NSE and Cyfra21-1,the results showed that the expression of PD-1 and PD-L1 were independent of the level of the three tumor markers in the blood,regardless of whether the expression threshold is 5%or 10%.To the follow-up deadline,35(87.5%)patients developed disease progression with a median progression-free survival(PFS)of 12.0 months.Univariate survival analysis revealed that PD-1 expression and tumor site were associated with PFS.When 5%was used as the critical value,the median PFS of patients with positive and negative PD-1 expression was 10.1 months and 14.0 months,respectively,and the median PFS of 10%as the critical value was 9.6 months and 13.2months,respectively.The PFS of PD-1 negative patients was longer than that of the positive patients,and the difference was statistically significant(5%as the expression threshold,?~2=5.717,P=0.017,HR=2.480;10%as the expression threshold,?~2=4.428,P=0.035,HR=2.145).The Kaplan-Meier survival curve showed that the median PFS of patients with upper and middle thoracic tumors was shorter than that of patients with lower thoracic segments.The difference was statistically significant(median PFS:11.3 months in the upper thoracic and middle segments;14.4 months in the lower thoracic region,P=0.041).Multivariate survival analysis of Cox regression model found that tumor site and PD-1 expression were independent prognostic factors for PFS in patients.Conclusion:PD-1 and PD-L1 are highly expressed in ESCC tumor tissues;PD-L1expression may deepen tumor invasion and promote local progression;Tumor location and PD-1 is an independent prognostic factor for PFS,whereas PD-L1 is not associated with PFS.