Expression And Clinical Significance Of HHLA2 And PD-L1 In Non-small Cell Lung Cancer

Objective: As important immune molecules in tumor microenvironment,human endogenous retrovirus subfamily H long terminal repeat associating protein 2(HHLA2)and programmed cell death-ligand 1(PD-L1)play important regulatory roles in tumor development and progression.In this study,roles of HHLA2 and PD-L1 in the development,progression,invasion and metastasis of non-small cell lung cancer(NSCLC)were explored by detecting their expression in NSCLC tissues and analyzing their correlation with the clinical pathological characteristics of NSCLC.Methods: Achieved paraffin-embedded NSCLC tissue blocks that were resected from 60 patients(30 with adenocarcinoma of lung and 30 with squamous lung carcinoma)in Pathology Department of the First Affiliated Hospital of Southwest Medical University from January 2015 to December 2015 were selected;based on the size of resected specimens,adjacent lung tissues>3cm away from the NSCLC tissues were selected from 30 patients(18 with squamous carcinoma and 12 with adenocarcinoma)as the adjacent tissue control group;all the included patients had no other pulmonary diseases or malignant tumors in any other tissues or organs,and had not received chemotherapy,radiotherapy,immunotherapy,or any other therapy for malignant tumor prior to surgery; another 30 pathologically confirmed normal lung tissues were selected as the normal control group.The IHC En Vision method was used to detect the expression of HHLA2 and PD-L1 in NSCLC tissues.HHLA2 and PD-L1 expression in NSCLC was compared across different ages,pathological types,stages,smoking status and genders.Results: 1.The expression rate of HHLA2 in NSCLC tissues was81.67%,which was significant higher than 13.33% in epithelial cells in adjacent lung tissues and 0.00% in epithelial cells in normal lung tissues,with statistically significant differences(P<0.05);there was no statistically significant difference in HHLA2 expression between epithelial cells in normal lung tissues and epithelial cells in adjacent lung tissues(P>0.05);HHLA2 expression was not correlated with clinical stage of NSCLC,lymph node metastasis,gender,age,smoking status,or pathological type.2.The expression rate of PD-L1 in NSCLC tissues was53.33%,which was significant higher than 0.00% in epithelial cells in adjacent lung tissues and 0.00% in epithelial cells in normal lung tissues,with statistically significant differences(P<0.05);PD-L1 expression was correlated with clinical stage of NSCLC(P<0.05)and lymph node metastasis(P<0.05),but not correlated with gender,age,smoking status,or pathological type.3.There was correlation between HHLA2 and PD-L1 expression in NSCLC tissues(r=0.503,P<0.01).Conclusion: 1.HHLA2 expression is significantly increased in NSCLC, which may provide a new target for immunologic test and therapy.2.PD-L1 expression is significantly increased in NSCLC,which is correlated with the TNM stage,indicating its significant role in the development,progression,invasion and metastasis of non-small cell lung cancer.3.There is positive correlation between HHLA2 and PD-L1 expression in NSCLC tissues,indicating their possible synergism in the development,progression,invasion and metastasis of non-small cell lung cancer.