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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1532658
This article is part of the Research Topic Drug Development for Pancreatic Cancer: Novel Targets, Drug Candidates and Mechanisms View all articles
SUMOylation substrate encoding genesRelated Genes as Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma with Functional Assessment of SAF-B2
Provisionally accepted- Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China
Background: Pancreatic ductal adenocarcinoma (PDAC) is highly malignant with a poor prognosis, posing significant clinical challenges. SUMOylation, a reversible post-translational modification, plays a critical role in tumor progression, yet its prognostic significance in PDAC remains unclear.We assessed SUMOylation expression patterns and function in PDAC using Western blot and the SUMOylation inhibitor TAK-981. Differentially expressed SUMOylation substrate encoding genesSUMOylation-related genes (DE-SSERGs) were identified from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression Project (GTEx) datasets. A SUMOylation-based prognostic model, Sscore, was constructed using LASSO and Cox regression. Additional analyses included somatic mutation, immune infiltration, TIDE, drug sensitivity, and single-cell RNA sequencing. The role of SAFB2 in PDAC was validated in vitro.Results: PDAC cells showed elevated SUMOylation, and its inhibition reduced cell proliferation. The Sscore model, based on DE-SSERGs (CDK1, AHNAK2, SAFB2), predicted overall survival and correlated with genome variation, immune infiltration, and drug sensitivity. Single-cell analysis further confirmed a link between high Sscore and malignancy. SAFB2, identified as a pivotal gene within the Sscore model, was significantly downregulated in PDAC tissues and cell lines; its overexpression was shown to inhibitsuppress PDAC cell proliferation, migration, and invasion. by suppressing the Wnt/β-Catenin signaling pathway.This study underscores the role of SUMOylation in PDAC and introduces the Sscore as a prognostic tool. SAFB2 is identified as a potential tumor suppressor, offering new therapeutic targets for PDAC.
Keywords: Pancreatic Ductal Adenocarcinoma Pancreatic carcinoma, Sumoylation, TAK-981, prognosis, SAFB2, Gene Expression Profiling, Tumor Microenvironment, Anticancer drug sensitivity tests Wnt/β-Catenin signaling pathway
Received: 22 Nov 2024; Accepted: 31 Mar 2025.
Copyright: © 2025 Wang, Yang, Liu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jian Wang, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, China
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