Objective To develop and validate a predicting model for prognosis of lung adenocarcinoma(LU AD).Methods R language was utilized for screening differentially expressed protein-coding genes(DEGs)obtained from the UCSC genome website.GO(Gene Ontology)and KEGG(Kyoto Encyclopedia of Genes and Genomes)pathway enrichment evaluations were used.A credible random split-sample method was used to divide data into training and validation dataset(split ratio=0.6∶0.4).Lasso(Least absolute shrinkage and selection operator)Logistic regression and random forest algorithm were applied to select predictors and develop the nomogram.The relationship between immune infiltration and prognosis of CACNA2D2 and CD79A was examined.The clinical usefulness of nomogram was also evaluated with ROC(receiver operating characteristic)and DCA(decision curve analysis)curves.The mRNA and protein expression levels of CACNA2D2 and CD79A in lung adenocarcinoma cells were analyzed by Western blotting and qRT-PCR assays.The expressions of CACNA2D2 and CD79A in 48 LUAD patients were detected by immunohistochemical staining.Results A total of 42 upregulated genes and 19 down regulated genes were identified.Only CACNA2D2 and CD79A were highly correlated with tumor stage and survival prognosis.Among them,the overexpression of CD79A was associated closely with immune response.LUAD patients with CACNA2D2 and CD79A low-expression had a significantly high risk of advanced N stage and worse overall survival(OS).Gene-based nomogram model was constructed,both ROC and DCA curves were used to verify model.Moreover,the expressions of CACNA2D2 and CD79A in lung adenocarcinoma cells were lower than that in bronchial epithelial cells,and negative expressions of CACNA2D2 and CD79A in LUAD tumor tissues were more common in stage Ⅲ-Ⅳ patients and patients with distant metastasis,while strong positive tumors of CACNA2D2 and CD79A were more common in stage Ⅰ-Ⅱ patients and patients without distant metastasis.Conclusion Low-expression CACNA2D2 and CD79A in tumor were associated with tumor stage and unfavorable overall survival in LUAD.CACNA2D2 and CD79A could be a potential predictor and therapeutic target in LUAD.