Expression And Clinical Significance Of Caspase-3/GSDME Mediated Pyroptosis Signaling Pathway In Non-small-cell Lung Cancer

Aim:Pyroptosis is a newly discovered type of programmed cell death with high inflammation,which plays a dual role in the development of cancer and malignant tumor.The purpose of this study was to investigate the role of caspase3/GSDME mediated pyroptosis in non-small cell lung cancer（NSCLC）,and to investigate the effect of inflammatory response induced by pyroptosis on NSCLC patients and its clinical significance.Method:We detected the expression of GSDME,caspase-3,HMGB1 in 120 cases of lung cancer and 40 cases of para-cancer tissues by immunohistochemical staining,and to analyze the relationship between GSDME、caspase-3、HMGB1 protein and clinical stage,pathological grade and survival prognosis of patients.In addition,by detected the accumulation and distribution differences of CD8⁺T cells and tumor-associated macrophages in cancer and adjacent tissues.The relationship between the abundance of CD8⁺T cells and tumor-associated macrophages and the expression levels of the above proteins was determined by statistical analysis.Result:1.The protein expression levels of GSDME and caspase-3,as well as the abundance of CD8⁺T cells and tumor-associated macrophages in non-small-cell lung cancer tissues were significantly higher than those in adjacent tissues,and the differences were statistically significant（P<0.05）.2.The expression of GSDME,caspase-3,HMGB1 and the abundance of CD8⁺T cells were the factors affecting the lymph node metastasis of non-small-cell lung cancer patients,and the difference between groups was statistically significant（p<0.05）.In addition,tumor size was also an important factor.Tumor size not only affects survival,but also affects the expression of caspase-3.The expression of caspase-3 was higher in the group with smaller tumor diameter,and the difference was statistically significant（P<0.05）.It is interesting that the high expression rate of HMGB1 in squamous-cell Carcinoma is higher than that in Adenocarcinoma,and the difference was statistically significant（P<0.05）.3.Spearman correlation analysis showed that GSDME was significantly positively correlated with the expressions of caspase-3、HMGB1,CD8⁺T cells and tumor-related macrophages（all P values were less than 0.05）.HMGB1 and caspase-3 were significantly correlated with CD8⁺T cell abundance.There was a significant positive correlation between the content of CD8⁺T cells and Tumor-associated macrophages（P<0.05）.4.Kaplan-Meier survival analysis showed that GSDME,caspase-3,HMGB1,the content of tumor-related macrophages,pathological tissue grade,clinical TNM stage,The presence or absence of lymph node metastasis and tumor size were all factors affecting the prognosis of patients.Age,gender,tumor type and smoking history were not associated with prognosis in this study（P<0.05）.5.GSDME and tumor diameter are independent factors affecting the prognosis and survival of non-small-cell lung cancer patients（P<0.05）.Conclusion:1.caspase-3/GSDME mediates pyroptosis in non-small-cell lung cancer.2.High expression of GSDME,caspase-3 and HMGB1 inhibits lymph node metastasis in patients with NSCLC,and these factors may play a role in inhibiting cancer as well as mediating pyroptosis.3.The abundance of CD8⁺T cells and tumor-associated macrophages increased after GSDME triggered pyroptosis.4.Pyroptosis and its secondary inflammatory response may play an important role in inhibiting cancer.