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Background: Dysregulation of the ubiquitin-proteasome system (UPS) can lead to instability in the cell cycle and may act as a crucial factor in both tumorigenesis and tumor progression. However, there is no established prognostic signature based on UPS genes (UPSGs) for lung adenocarcinoma (LUAD) despite their value in other cancers.Methods: We retrospectively evaluated a total of 703 LUAD patients through multivariate Cox and Lasso regression analyses from two datasets, the Cancer Genome Atlas (n = 477) and GSE31210 (n = 226). An independent dataset (GSE50081) containing 128 LUAD samples were used for validation.Results: An eight-UPSG signature, including ARIH2, FBXO9, KRT8, MYLIP, PSMD2, RNF180, TRIM28, and UBE2V2, was established. Kaplan-Meier survival analysis and time-receiver operating characteristic curves for the training and validation datasets revealed that this risk signature presented with good performance in predicting overall and relapsed-free survival. Based on the signature and its associated clinical features, a nomogram and corresponding web-based calculator for predicting survival were established. Calibration plot and decision curve analyses showed that this model was clinically useful for both the training and validation datasets. Finally, a web-based calculator (https://ostool.shinyapps.io/lungcancer) was built to facilitate convenient clinical application of the signature.Conclusion: An UPSG based model was developed and validated in this study, which may be useful as a novel prognostic predictor for LUAD. |
