Identification of a four-gene panel predicting overall survival for lung adenocarcinoma
Abstract Object Lung cancer is the most frequently diagnosed carcinoma and the leading cause of cancer-related mortality. Although molecular targeted therapy and immunotherapy have made great progress, the overall survival (OS) is still poor due to a lack of accurate and available prognostic biomarkers. Therefore, in this study we aimed to establish a multiple-gene panel predicting OS for lung adenocarcinoma. Methods We obtained the mRNA expression and clinical data of lung adenocarcinoma (LUAD) from TCGA database for further integrated bioinformatic analysis. Lasso regression and Cox regression were performed to establish a prognosis model based on a multi-gene panel. Nomogram was built based on the model. The receiver operating characteristic (ROC) curve and the Kaplan–Meier curve were used to assess the predicted capacity of the model. The prognosis value of the multi-gene panel was further validated using a dataset from GEO. Gene set enrichment analysis (GSEA) was performed to explore potential biological mechanisms of a novel prognostic gene signature. Results A four-gene panel (including DKK1, GNG7, LDHA, MELTF) was established as a prognostic indicator for OS of LUAD. The ROC curve revealed good predicted performance in both test cohort (AUC = 0.740) and validation cohort (AUC = 0.752). Each patient was calculated a risk score according to the model based on the four-gene panel. The results showed that the risk score was an independent prognostic factor, and the high-risk group had a worse OS compared with the low-risk group. The nomogram based on this model shows better prediction performance. GNG7 was decreased in LUAD and its mRNA expression was negatively correlated with the DNA methylation level. GSEA demonstrated the main enrichment pathways of GNG7 were cell cycle, RNA degradation, DNA replication, et al. Conclusion Our study proposed a novel four-gene panel to predict the OS of LUAD, which may contribute to predicting prognosis accurately and making the clinical decisions of individual therapy for LUAD patients. GNG7 might act a crucial role in genesis and progression of LUAD.