SUMOylation substrate encoding genes as prognostic biomarkers in pancreatic ductal adenocarcinoma with functional assessment of SAF-B2
BackgroundPancreatic 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.MethodsW...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1532658/full |
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| author | Xiangjun Wang Chuanxin Yang Yangming Liu Jian Wang |
| author_facet | Xiangjun Wang Chuanxin Yang Yangming Liu Jian Wang |
| author_sort | Xiangjun Wang |
| collection | DOAJ |
| description | BackgroundPancreatic 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.MethodsWe assessed SUMOylation expression patterns and function in PDAC using Western blot and the SUMOylation inhibitor TAK-981. Differentially expressed SUMOylation substrate encoding genes (DE-SSEGs) 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.ResultsPDAC cells showed elevated SUMOylation, and its inhibition reduced cell proliferation. The Sscore model, based on DE-SSEGs (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 inhibit PDAC cell proliferation, migration, and invasion by suppressing the Wnt/β-Catenin signaling pathway.ConclusionThis 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. |
| format | Article |
| id | doaj-art-6b412de9d7584df2b5248db205d3ad5e |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-6b412de9d7584df2b5248db205d3ad5e2025-08-20T02:26:24ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-04-011610.3389/fphar.2025.15326581532658SUMOylation substrate encoding genes as prognostic biomarkers in pancreatic ductal adenocarcinoma with functional assessment of SAF-B2Xiangjun WangChuanxin YangYangming LiuJian WangBackgroundPancreatic 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.MethodsWe assessed SUMOylation expression patterns and function in PDAC using Western blot and the SUMOylation inhibitor TAK-981. Differentially expressed SUMOylation substrate encoding genes (DE-SSEGs) 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.ResultsPDAC cells showed elevated SUMOylation, and its inhibition reduced cell proliferation. The Sscore model, based on DE-SSEGs (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 inhibit PDAC cell proliferation, migration, and invasion by suppressing the Wnt/β-Catenin signaling pathway.ConclusionThis 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.https://www.frontiersin.org/articles/10.3389/fphar.2025.1532658/fullPancreatic ductal adenocarcinomaSUMOylationTAK-981PrognosisSAFB2Wnt/β-Catenin signaling pathway |
| spellingShingle | Xiangjun Wang Chuanxin Yang Yangming Liu Jian Wang SUMOylation substrate encoding genes as prognostic biomarkers in pancreatic ductal adenocarcinoma with functional assessment of SAF-B2 Frontiers in Pharmacology Pancreatic ductal adenocarcinoma SUMOylation TAK-981 Prognosis SAFB2 Wnt/β-Catenin signaling pathway |
| title | SUMOylation substrate encoding genes as prognostic biomarkers in pancreatic ductal adenocarcinoma with functional assessment of SAF-B2 |
| title_full | SUMOylation substrate encoding genes as prognostic biomarkers in pancreatic ductal adenocarcinoma with functional assessment of SAF-B2 |
| title_fullStr | SUMOylation substrate encoding genes as prognostic biomarkers in pancreatic ductal adenocarcinoma with functional assessment of SAF-B2 |
| title_full_unstemmed | SUMOylation substrate encoding genes as prognostic biomarkers in pancreatic ductal adenocarcinoma with functional assessment of SAF-B2 |
| title_short | SUMOylation substrate encoding genes as prognostic biomarkers in pancreatic ductal adenocarcinoma with functional assessment of SAF-B2 |
| title_sort | sumoylation substrate encoding genes as prognostic biomarkers in pancreatic ductal adenocarcinoma with functional assessment of saf b2 |
| topic | Pancreatic ductal adenocarcinoma SUMOylation TAK-981 Prognosis SAFB2 Wnt/β-Catenin signaling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1532658/full |
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