Correlation And Prognosis Between Snail And The Expression Of PDL1 And CD8⁺T In Esophageal Squamous Cell Carcinoma

BackgroundEsophageal squamous cell carcinoma（ESCC）is the most common malignant tumor in the world.Early symptoms are insidious and highly invasive,and local infiltration or distant metastasis often exists at the time of diagnosis,which is the main cause of death of Esophageal squamous cell carcinoma^[1].At present,no specific biomarkers have been found to accurately predict the prognosis of patients with esophageal squamous cell carcinoma,which limits clinical monitoring,treatment guidance and disease evaluation.Therefore,it is particularly important to find biomarkers related to the prognosis of patients with esophageal squamous cell carcinoma.Studies have shown that tumor metastasis is closely related to immunosuppression,both of which can have a profound impact on the prognosis of patients.In previous studies on the role of PLCE1 in metastasis and invasion of esophageal squamous cell carcinoma,our research group found that PLCE1 plays a role in promoting metastasis by stabilizing Snail transcriptional activity,suggesting that Snail plays a significant role in metastasis of esophageal squamous cell carcinoma^[2].Is there a connection between PDL1 and CD8⁺T,which are important participants in tumor immunosuppression?Therefore,from the perspective of tumor immunity,this study will explore the correlation and clinical significance of Snail with immune factors PDL1 and CD8⁺T,which has not been reported in esophageal squamous cell carcinoma.ObjectiveThis study aims to explore the correlation between Snail and PDL1 and CD8⁺T expression in esophageal squamous cell carcinoma and its clinical significance,which provides a new research direction for the prognosis assessment of esophageal squamous cell carcinoma patients.MethodsAll subjects were recruited from patients who were diagnosed with esophageal squamous cell carcinoma after surgery in the Department of General Surgery of the First Affiliated Hospital of Xinxiang Medical College between February 2014 and December2015.According to the inclusion criteria,222 cases were included as subjects,and relevant clinical data and follow-up were collected.The esophageal squamous cell carcinoma tissues were detected by immunohistochemistry,and the data were statistically analyzed by SPSS 25.0 software.Results1.In 222 cases of ESCC,Snail was mainly expressed in the nucleus,CD8⁺T was expressed in the cell membrane,and PDL1 was expressed in the tumor cell membrane,plasm and immune stroma.2.In 222 cases of ESCC,Snail protein expression and its differentiation（χ2=5.204,P=0.022）,and infiltration depth（χ2=8.655,P=0.003）,and lymph node metastasis（χ2=19.007,P<0.001）,and distant metastasis（χ2=9.184,P=0.001）,and TNM stage（χ2=24.065,P=0.001）associated with;The positive and negative expression of PDL1 protein was correlated with the degree of differentiation（χ2=9.018,P=0.003）,lymph node metastasis（χ2=4.084,P=0.043）,and TNM stage（χ2=8.409,P=0.004）.The expression of CD8⁺T lymphocyte infiltration was only associated with the age of patients（χ2=5.595,P=0.018）.3.COX risk regression analysis of 222 ESCC tissues showed that distant metastasis（HR=4.060,P<0.001）,and degree of differentiation（HR=1.562,P=0.018）,and depth of invasion（HR=2.053,P=0.001）,and lymph node metastasis（HR=3.664,P<0.001）,and TNM stage（HR=4.162,P<0.001）,and CD8⁺T low infiltration expression（HR=0.605,P=0.008）,and Snail protein expression（HR=3.781,P<0.001）was a prognostic risk factor,and only Snail protein was expressed（HR=2.342,P<0.001）and TNM stage（HR=3.464,P<0.001）was an independent risk factor for the prognosis of ESCC.4.Spearman correlation analysis of 222 ESCC showed that Snail was significantly positively correlated with PDL1 expression（r=0.210,P=0.002）,and negatively correlated with CD8⁺T cell infiltration（r=-0.174,P=0.009）,PDL1 was positively correlated with CD8⁺T expression（r=0.293,P<0.001）.5.Kaplan-Meier survival analysis of 222 cases of ESCC showed that Overall survival（OS）of patients with high Snail protein expression group was significantly shorter than that of patients with low Snail protein expression group（P<0.0001）;although the overall survival of patients with PDL1-positive expression showed a worse trend,it did not reach statistical significance（P=0.156）;The survival curve of Snail/PDL1 combined test showed no significant difference compared with that of Snail alone（P>0.05）,but based on the status of low infiltration expression of CD8⁺T cells,there was a significant difference in the survival curve of the combined detection of CD8⁺T cells compared with the single detection of Snail（P=0.015）;The survival curve of the combined detection of the three was significantly different from that of the single detection of Snail（P=0.015）.Conclusions1.In this study,the correlation between Snail and PDL1 and CD8⁺T was revealed for the first time in esophageal squamous cell carcinoma.Snail/PDL1/CD8⁺T combined detection can serve as an important reference for prognosis assessment of patients with esophageal squamous cell carcinoma.2.Snail inhibition may serve as a multi-benefit target for simultaneously breaking multiple immunosuppressive pathways,which will provide a new direction for immunotherapy of patients with esophageal squamous cell carcinoma.