Analysis The Expression And Its Association Of PKM2 And PD-L1 In Lung Cancer Patients

Backgroundlung cancer is characterized by the most morbidity and mortality rate in the world.More than 60%patients in the initial diagnosis have been in locally advanced or metastatic stage,leading to a high recurrence rate and low 5-year survival rate.Although targeted therapy and immunotherapy have brought benefits to patients with advanced lung cancer,only a small number of patients could obtain a benefit and drug resistance was inevitable.Therefore,it is necessary to further investigate the development mechanism of lung cancer to maximize the benefit of patients.More and more studies suggest that pyruvate kinase M2(PKM2)is involved in the development of lung cancer through multiple mechanisms;however,it is unclear whether PKM2 could contribute to tumor development via inducing tumor immune escape.ObjectiveThis study was to detect the PKM2 expression in lung cancer patients and further assess the relationship between PKM2 expression and the clinical pathological features,as well as PD-L1 expression.Moreover,present study preliminaryly explorated whether PKM2 contributed to lung cancer occurrence and development by inducing tumor cell membrane programmed death-ligand 1(PD-L1)expression.Methods(1)this paper discussed PKM2 expression in lung cancer through immunohist-ochemical technique and analyzed the association bettween PKM2 expression and clinical pathological features,as well as PD-L1 expression by the chi-square test and Spearsman nonparametric correlation analysis.(2)this paper used the shRNA-PKM2 lentivirus to transfect A549 cell line and tested the expression of PD-L1 in mRNA,total protein and cell membrane level through quantitative polymerase chain reaction,Western blotting and fluid cytology technology,respectively.Results1.The relationship between PKM2 and clinical pathological features of lung cancer patients.High PKM2 expression in patients with lung cancer was significantly associated with clinical stage(P= 0.017),T classification(P = 0.029)and N classification(P ?0.008),regardless of M classification.2.The expression of PKM2 is closely related to PD-L1 expression.In patients with high PKM2 expression,the positive rate of PD-L1 expression was 53.1%,whereas in patients with low PKM2 expression,the positive rate was only 22.7%(P = 0.033).Moreover,Spearman rank correlation analysis further revealed that PKM2 expression was linearly positive with PD-L1 expression(correlation coefficient 0.367,P = 0.002).3.PKM2 affects PD-L1 expression.After transfection with shRNA-PKM2 in A549 cell line,the expression of PD-L1 mRNA in transfection group was significantly higher while the totol protein of PD-L1 was significantly lower,compared with control group.It is suggested that post transcriptional modification is involved in the regulation of the expression of PD-L1 by PKM2.Subsequently,flow cytometry implied that the expression of PD-L1 in cell membrane was significantly lower in transfection group than control group.ConclusionThis study found that high PKM2 expression closely associated with aggressive clinicopathological features in patients with lung cancer and PKM2 mediated tumor immune escape through regulating PD-L1 expression.These findings are important to further understand the mechanism of PKM2 in occurrence and development of lung cancer.