An Immune-related Gene Prognostic Index For Lung Adenocarcinoma

Objective To construct an immune-related gene prognosis index（IRGPI）for lung adenocarcinoma to predict the effect of conventional immune checkpoint inhibitor（ICI）treatment,and to screen biomarkers that can predict the prognosis of lung adenocarcinoma patients.Methods By using R package,we carried out weighted gene co-expression network analysis,protein-protein interaction network analysis,functional enrichment analysis,survival analysis,and gene set enrichment analysis,and finally carried out verification using cell experiments.Results Based on the lung adenocarcinoma dataset in the Cancer Genome Atlas（TCGA）,we first obtained 407 immune-related differentially expressed genes（75 up-regulated and 332 down-regulated）.These genes were analyzed by WGCNA,PPI and survival,and finally 36 Hub genes related to prognosis were identified.Subsequently,an IRGPI was constructed based on seven prognosis-related Hub genes:CAMP,NOS1,PLK1,CD 19,KIR2DL3,KL,and TNFSF11.With the median value of IRGPI score as the boundary,the patients with different IRGPI scores were divided into an IRGPI high group and an IRGPI low group.The patients with lung adenocarcinoma with high IRGPI score had worse prognosis and higher tumor mutation burden（TMB）,suggesting that the IRGPI score might be related to the prediction of ICI treatment effect.Subsequently,a comparison of tumor immune dysfunction and exclusion（TIDE）scores between the IRGPI high group and the IRGPI low group revealed that the IRGPI high group had a lower TIDE score,further suggesting that patients with lung adenocarcinoma with a high IRGPI score benefited more from ICI therapy.Finally,the PLK1 gene with the highest hazard ratio（HR）value was screened out from the IRGPI model and subjected to survival analysis and cellular experimental verification.The results showed that PLK1 was a potential biomarker for predicting the prognosis of patients.Conclusion IRGPI is a potential prognostic indicator for lung adenocarcinoma patients treated with ICI,and PLK1 gene that can predict the prognosis of patients has been screened out from the IRGPI model.