Dataset Information

Establishment and validation of a ubiquitination-related gene signature associated with prognosis in pancreatic duct adenocarcinoma.

ABSTRACT:

Background

Patients with pancreatic duct adenocarcinoma (PDAC) have varied prognoses that depend on numerous variables. However, additional research is required to uncover the latent impact of ubiquitination-related genes (URGs) on determining PDAC patients' prognoses.

Methods

The URGs clusters were discovered via consensus clustering, and the prognostic differentially expressed genes (DEGs) across clusters were utilized to develop a signature using a least absolute shrinkage and selection operator (LASSO) regression analysis of data from TCGA-PAAD. Verification analyses were conducted across TCGA-PAAD, GSE57495 and ICGC-PACA-AU to show the robustness of the signature. RT-qPCR was used to verify the expression of risk genes. Lastly, we formulated a nomogram to improve the clinical efficacy of our predictive tool.

Results

The URGs signature, comprised of three genes, was developed and was shown to be highly correlated with the prognoses of PAAD patients. The nomogram was established by combining the URGs signature with clinicopathological characteristics. We discovered that the URGs signature was remarkably superior than other individual predictors (age, grade, T stage, et al). Also, the immune microenvironment analysis indicated that ESTIMATEscore, ImmuneScores, and StromalScores were elevated in the low-risk group. The immune cells that infiltrated the tissues were different between the two groups, as did the expression of immune-related genes.

Conclusion

The URGs signature could act as the biomarker of prognosis and selecting appropriate therapeutic drugs for PDAC patients.

SUBMITTER: Guo Y

PROVIDER: S-EPMC10289160 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Establishment and validation of a ubiquitination-related gene signature associated with prognosis in pancreatic duct adenocarcinoma.

Guo Yangyang Y Wu Zhixuan Z Cen Kenan K Bai Yongheng Y Dai Ying Y Mai Yifeng Y Hong Kai K Qu Liangchen L

Frontiers in immunology 20230609

<h4>Background</h4>Patients with pancreatic duct adenocarcinoma (PDAC) have varied prognoses that depend on numerous variables. However, additional research is required to uncover the latent impact of ubiquitination-related genes (URGs) on determining PDAC patients' prognoses.<h4>Methods</h4>The URGs clusters were discovered via consensus clustering, and the prognostic differentially expressed genes (DEGs) across clusters were utilized to develop a signature using a least absolute shrinkage and ...[more]

PMID: 37359528

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Project description:Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancy with poor prognosis. To improve patient outcomes, it is necessary to gain a better understanding of the oncogenesis and progression of this disease. Metabolic reprogramming, particularly the regulation of lactate metabolism, is known to have a significant impact on tumor microenvironment and could provide valuable insights for the management of PDAC patients. In this study, we aimed to investigate the prognostic potential of lactate metabolism-related genes (LMRGs). Methods: Transcriptomic data of patients with PDAC along with the clinical outcomes were retrieved from The Cancer Genome Atlas database, and the expression data in normal pancreas from Genotype-Tissue Expression dataset were adopted as the normal control. By using Cox and LASSO regression models, we identified key genes that are differentially expressed in cancerous tissues and related to prognosis. To determine the prognostic value of LMRGs in PDAC, we evaluated their clinical significance and model performance using both the area under the receiver operator characteristic curve (AUC) and calibration curves. In addition, we evaluated the drug sensitivity prediction and immune infiltration by using oncoPredict algorithm, single sample gene set enrichment analysis and Tumor Immune Estimation Resource. Results: A total of 123 LMRGs were identified through differential gene screening analysis, among which 7 LMRGs were identified to comprise a LMRGs signature that independently predict overall survival of these PDAC patient. The AUC values for the LMRGs signature were 0.786, 0.820, 0.837, and 0.816 for predicting 1-, 2-, 3- and 5-year overall survival respectively. Furthermore, this prognostic signature was used to stratify patients into high-risk and low-risk groups, with the former having worse clinical outcomes. This observation was further validated through analysis of the International Cancer Genome Consortium database. In addition, lower sensitivity to gemcitabine and infiltration of immune effector cells were observed in the cancer tissue of patients in the high-risk group. Conclusion: In conclusion, our data suggests that a genomic signature comprised of these LMRGs may be a novel predictor of overall clinical outcomes and present therapeutic potential for PDAC patients.

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Dataset Information

Establishment and validation of a ubiquitination-related gene signature associated with prognosis in pancreatic duct adenocarcinoma.

Background

Methods

Results

Conclusion

Publications

Establishment and validation of a ubiquitination-related gene signature associated with prognosis in pancreatic duct adenocarcinoma.

Similar Datasets

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