ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Metabolism
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1615898
This article is part of the Research TopicSynthetic Biology and Metabolomics: Novel Insight in Oncology ResearchView all 7 articles
Pan-Cancer Landscape of UBD/FAT10 and Experimental Validation in Esophageal Carcinoma
Provisionally accepted
- Lu'an People's Hospital, Lu'an, China
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Objective: To comprehensively characterize the pan-cancer roles of Ubiquitin D (UBD/FAT10) in tumorigenesis, immune regulation, and therapeutic response through integrative multi-omics and experimental analyses. Methods: Utilizing bulk RNA-seq (TCGA/GTEx/CPTAC), immune deconvolution, proteomics, and functional enrichment, we analyzed UBD expression, survival prognosis, immune infiltration, and molecular pathways across 33 cancers. Molecular docking and MD simulations were performed to assess UBD-protein interactions. Through lentivirus-mediated overexpression, functional assays (CCK-8, colony formation, wound healing, and Transwell), transcriptome sequencing, and biochemical validation, we demonstrated that UBD promotes malignant phenotypes in esophageal cancer via the TP53 signaling pathway. Results:UBD was upregulated in 14 cancers but downregulated in thyroid carcinoma (THCA) and kidney chromophobe (KICH). ROC analysis highlighted UBD's diagnostic potential (AUC >0.8 in gastrointestinal tumors). High UBD conferred protection in melanoma (SKCM, HR=0.891) and sarcoma (SARC, HR=0.899) but predicted poor outcomes in uveal melanoma (UVM, HR=1.298) and pancreatic adenocarcinoma (PAAD, HR=1.143).UBD positively correlated with the IFN-γ-dominant immune subtype (C2), characterized by CD8+ T cells/M1 macrophages. Drug sensitivity profiling nominated imatinib (Vina score: -8.9 kcal/mol) and TTNPB as potential therapies for UBD-high tumors, validated by stable MD simulations.In esophageal carcinoma (ESCA), UBD expression escalated with tumor stage and predicted poor survival (p<0.05).UBD enhances the proliferation and migration of esophageal cancer cells by modulating the TP53 signaling pathway, as validated through transcriptomic analysis and functional assays. Conclusions: This study advances UBD as a prognostic indicator and therapeutic target, bridging molecular insights with clinical translation in precision oncology.
Keywords: ubiquitin D, Cancer, TCGA, immune, pancancer
Received: 22 Apr 2025; Accepted: 30 Sep 2025.
Copyright: © 2025 Zhang, Pan 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: Xiuzhong Wang, xiuzhongwang@email.cn
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