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Multi-omics and experimental validation identify USP54 as a prognostic deubiquitinase promoting pancreatic ductal adenocarcinoma progression within the immune microenvironment

By: Zibo Yuan · Zhiwei Yu · Qiuran Xu · Dongsheng Huang · Di Cui

3 April 2026 at 18:00

Front Immunol. 2026 Mar 18;17:1791707. doi: 10.3389/fimmu.2026.1791707. eCollection 2026.

ABSTRACT

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a complex tumor ecosystem that contributes to its progression. Deubiquitinases (DUBs) are vital regulators in cancer. However, the overall activity of DUBs and their role in driving PDAC progression within immune microenvironment remain largely unknown.

METHODS: We employed an integrative multi-omics strategy combining machine learning (ML) on bulk transcriptomic data, single-cell RNA sequencing and spatial transcriptomic profiling. We applied Coxnet and Fuzzy SVM for prognostic modeling, inferCNV for malignant cell identification, SCENIC for transcription factor regulon analysis, LIANA⁺ for inferring inter-cellular communication networks and cell2location for spatial deconvolution. USP54 expression was detected by real-time quantitative PCR, western blotting and immunohistochemistry. USP54 function was validated through in vitro and in vivo assays.

RESULTS: ML-based pathway analysis revealed post-translational modification as a major prognostic category, within which elevated DUBs activity emerged as an independent adverse prognostic factor. At the single-cell level, USP54 was upregulated along the trajectory of malignant ductal cells and correlated with an inflamed tumor microenvironment. Cell-cell communication analysis predicted signaling from monocytes/macrophages to tumor cells via the THBS1-integrin ligand-receptor pair. This immune-derived signaling potentially converged on KLF5-positive tumor cells, with KLF5 identified as a putative transcriptional activator of USP54. Spatial transcriptomics validated the co-localization of USP54 expression, elevated DUB activity, and KRAS signaling within specific tumor niches adjacent to THBS1-enriched immune regions. High USP54 expression was frequently observed in PDAC tissues and associated with poor patient survival. More importantly, in both BxPC-3 and PANC-1 cell lines, USP54 knockdown suppressed cell proliferation and metastasis, whereas its overexpression enhanced these malignant phenotypes. Subcutaneous xenograft growth and tail vein injection experiments validated these findings in vivo.

CONCLUSIONS: Our comprehensive multi-omics analysis and experimental validation identify the deubiquitinase USP54 as a novel promoter of PDAC progression within a spatially organized tumor-immune microenvironment. These findings suggest USP54 as both a candidate prognostic biomarker and a potential therapeutic target for this lethal malignancy.

PMID:41929495 | PMC:PMC13038871 | DOI:10.3389/fimmu.2026.1791707

MM-ReCoder: Advancing Chart-to-Code Generation with Reinforcement Learning and Self-Correction

cs.AI, q-bio.NC updates on arXiv.org

By: Zitian Tang · Xu Zhang · Jianbo Yuan · Yang Zou · Varad Gunjal · Songyao Jiang · Davide Modolo

3 April 2026 at 12:00

arXiv:2604.01600v1 Announce Type: new Abstract: Multimodal Large Language Models (MLLMs) have recently demonstrated promising capabilities in multimodal coding tasks such as chart-to-code generation. However, existing methods primarily rely on supervised fine-tuning (SFT), which requires the model to learn code patterns through chart-code pairs but does not expose the model to a code execution environment. Moreover, while self-correction through execution feedback offers a potential route to improve coding quality, even state-of-the-art MLLMs have been shown to struggle with effective self-correction. In this work, we introduce MM-ReCoder, a chart-to-code generation model trained with reinforcement learning (RL) and equipped with self-correction ability. We propose a two-stage multi-turn self-correction RL strategy based on Group Relative Policy Optimization (GRPO). The first stage enhances the model's self-correction ability via rolling out a shared first turn, while the second stage improves the coding capability with full-trajectory optimization. MM-ReCoder learns to produce more accurate and executable code through the interaction with the environment and by iteratively correcting its own outputs. Our results on three chart-to-code benchmarks demonstrate the state-of-the-art performance of MM-ReCoder.