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

Yangyang Guo; Zhixuan Wu; Kenan Cen; Yongheng Bai; Ying Dai; Yifeng Mai; Kai Hong; Liangchen Qu

doi:10.3389/fimmu.2023.1171811

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

Front Immunol. 2023 Jun 9:14:1171811. doi: 10.3389/fimmu.2023.1171811. eCollection 2023.

Authors

Yangyang Guo^{1

2}, Zhixuan Wu³, Kenan Cen¹, Yongheng Bai⁴, Ying Dai¹, Yifeng Mai¹, Kai Hong¹, Liangchen Qu²

Affiliations

¹ Department of General Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, China.
² Department of Emergency, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China.
³ Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁴ National Key Clinical Specialty (General Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

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.

Keywords: PDAC; immune microenvironment; immunotherapy; prognosis; ubiquitination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Pancreatic Ductal* / genetics
Humans
Pancreatic Ducts
Pancreatic Neoplasms* / genetics
Prognosis
Tumor Microenvironment / genetics
Ubiquitination

Grants and funding

This study was sponsored by the Ningbo University Institute of Geriatrics (LNBYJS-2021), Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province (2018E10008) and the Wenzhou Municipal Science and Technology Plan Project (Y20220185).