Construction of ubiquitination-related risk model for predicting prognosis in lung adenocarcinoma

Q: Which genes are linked to prognosis in the study, and how was validation performed?

Upregulation of STC1, UBE2S, and DTL is associated with worse prognosis, while CISH upregulation is associated with better prognosis. RT-qPCR was performed as experimental validation.

Sep 23, 2026

Uploaded by Margaret

Construction of a ubiquitination-based gene signature for lung adenocarcinoma prognosis uses the TCGA-LUAD cohort as training and multiple survival modeling approaches to identify ubiquitination-related genes, compute ubiquitination-related risk scores, and stratify patients. High URRS associates with worse overall outcomes and is validated across six external cohorts. The high-risk group shows elevated PD1/L1, TMB, TNB, and TME features, lower chemotherapy IC50 values, and distinct gene-level validation by RT-qPCR, supporting biomarker potential for prognosis and treatment guidance.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages18

Reading Time45 min

AccessFree to download

Introduction

Background on lung adenocarcinoma and ubiquitination

Methods

Cohort, gene selection, and risk score construction

Results

Prognosis stratification and validation

Associations with immune features and chemotherapy response

Gene-specific findings and RT-qPCR validation

Conclusion

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Construction of ubiquitinationrelated risk model for predicting prognosis in lung adenocarcinoma Dawei Sun1,2,3,4, Xiaohong Duan1,2,3, Ning Li1,2,3, Ou Qiao1,2,3, Yingjie Hou1,2,3, Zihuan Ma4, Siyao Liu4, Yanhua Gong1,2,3􀀍 & Zichuan Liu5,6􀀍 Lung adenocarcinoma is the most prevalent lung cancer type. Ubiquitination, a critical posttranslational modification process that regulates protein degradation and signaling pathways, has been implicated in various cancers, including LUAD. We aimed to explore the associations between ubiquitination and lung adenocarcinoma. TCGA-LUAD cohort served as the training set. Unsupervised clustering, univariate Cox regression, Random Survival Forests, and least absolute shrinkage and selection operator (LASSO) Cox regression were applied to identify ubiquitination-related genes (URGs), then ubiquitination-related risk scores (URRS) were calculated using gene expression and the univariate Cox’s coefficient. Comparisons between the high and the low URRS group regarding chemotherapy drug response, immune infiltration level, tumor mutation burden (TMB), tumor neoantigen load (TNB), PD1/L1 expression, and enriched pathways were performed. URRS was calculated based on the expression of DTL, UBE2S, CISH, and STC1 . Patients with higher URRS hada worse prognosis (Hazard Ratio [HR] = 0.54, 95% Confidence Interval [CI]: 0.39–0.73, p < 0.001), and the prognosis of the URRS was further confirmed in 6 external validation cohorts (Hazard Ratio [HR] = 0.58, 95% Confidence Interval [CI]: 0.36–0.93, pmax = 0.023). The high URRS group had higher PD1/L1 expression level (p < 0.05), TMB (p < 0.001), TNB (p < 0.001), and TME scores (p < 0.001). The IC50 values of various chemotherapy drugs were lower in the high URRS group. In addition, we found that upregulation ofSTC1, UBE2S, and DTL was associated with worse, while upregulation ofCISH was associated with better prognosis. We also performed a reverse transcription-quantitative polymerase chain reaction (RT-qPCR) for validation. In conclusion, the ubiquitination-based signature might serve as a biomarker to help evaluate the prognosis, biological features, and appropriate treatment for patients with lung adenocarcinoma. Keywords Lung adenocarcinoma, Ubiquitination, Immunotherapy, Prognosis, Biomarker, Chemotherapy Non-small cell lung cancers (NSCLCs) are malignant tumors, representing approximately 85% of all cases1. Among the various histological subtypes, lung adenocarcinoma (LUAD) is the most frequently diagnosed, accounting for over 40% of NSCLC cases and exhibiting a rising incidence in both smokers and non-smokers2. Global epidemiological data indicate that LUAD is a leading cause of cancer-related mortality, with an estimated 1.8 million deaths annually, driven by its high metastatic potential and molecular heterogeneity3. Despite advancements in targeted therapies and immune checkpoint inhibitors, the 5-year survival rate for advanced LUAD remains below 20%, underscoring the urgent need for improved prognostic biomarkers4,5. Ubiquitin–proteasome system (UPS), present in all eukaryotes, is a specialized proteolysis system that affects multiple cellular protein processes, including cell signaling, receptor trafficking, cell cycle, and immune response6. The ubiquitination process impacts the progression of cancer through multiple pathways, regulating disease progression both in tumor-promoting and tumor-inhibiting pathways. In non-small cell lung cancer (NSCLC), various ubiquitination pathways have been reported to be associated with its occurrence and development7,8. For instance, mutations in KRAS are common in NSCLC, and disruptions in the ubiquitination pathways that regulate KRAS protein stability can lead to its prolonged activity. This sustained activity drives 1School of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin University, No. 92 Weijin Road, N

FAQs

Which genes are linked to prognosis in the study, and how was validation performed?

Upregulation of STC1, UBE2S, and DTL is associated with worse prognosis, while CISH upregulation is associated with better prognosis. RT-qPCR was performed as experimental validation.

Sep 23, 2026

Uploaded by Margaret