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Pan-Cancer Landscape of the Novel Oxygen Sensor ADO and Its Potential Role in Hepatocellular Carcinoma

By: Jie Huang · Ying Xu · Yuqing Wang · Yuzhou Nie · Yidan Chen · Juan Shen · Shenglin Ma · Xueqin Chen

30 September 2026 at 18:00

J Hepatocell Carcinoma. 2026 Sep 24;13:637010. doi: 10.2147/JHC.S637010. eCollection 2026.

ABSTRACT

BACKGROUND: Hypoxia is a key driver of tumor progression across cancers, yet oxygen-sensing mechanisms beyond HIFs remain underexplored. 2-Aminoethanethiol dioxygenase (ADO) has recently been identified as an oxygen sensor, but its role in malignancy is poorly defined. We conducted a pan-cancer analysis of ADO with a special focus on hepatocellular carcinoma (HCC), to assess its oncogenic significance and clinical potential.

METHODS: A multi-omics pan-cancer analysis of ADO expression and survival was performed using TCGA and GTEx, with validation in HCC across ICGC, GEO, and CNHPP proteomic cohorts. Correlations with genetic, epigenetic, immune, and pathways were evaluated. Drug sensitivity was predicted. Functional validation was conducted in HCC cells through proliferation, colony formation, Western blotting, and xenograft assays.

RESULTS: ADO was aberrantly expressed across cancers and showed cancer type-specific survival associations. Integrative analyses revealed links with tumor mutation burden, microsatellite instability, chromatin regulator methylation, RNA modification, proliferative signaling (G2M checkpoint, MYC, TGF-β), an immunosuppressive microenvironment, and negative correlations with ROS-responsive genes. In HCC, ADO was consistently overexpressed, associated with advanced stage, poor differentiation, residual disease, and unfavorable survival across independent cohorts. ADO-high HCC showed reduced predicted responsiveness to checkpoint blockade but increased sensitivity to sorafenib and fluorouracil. Experimentally, ADO overexpression activated ERK signaling, upregulated CD276 and HMGB1, and promoted HCC cell proliferation, while ADO depletion suppressed tumor growth in vitro and in vivo, reversible upon re-expression.

CONCLUSION: ADO plays oncogenic and immunomodulatory roles in HCC, and may serve as a potential prognostic biomarker and therapeutic target in liver cancer.

PMID:42812529 | PMC:PMC13620309 | DOI:10.2147/JHC.S637010

OpenSage: Self-programming Agent Generation Engine

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

By: Hongwei Li · Zhun Wang · Qinrun Dai · Yuzhou Nie · Jinjun Peng · Ruitong Liu · Jingyang Zhang · Kaijie Zhu · Jingxuan He · Lun Wang · Yangruibo Ding · Yueqi Chen · Wenbo Guo · Dawn Song

16 March 2026 at 12:00

arXiv:2602.16891v2 Announce Type: replace Abstract: Agent development kits (ADKs) provide effective platforms and tooling for constructing agents, and their designs are critical to the constructed agents' performance, especially the functionality for agent topology, tools, and memory. However, current ADKs either lack sufficient functional support or rely on humans to manually design these components, limiting agents' generalizability and overall performance. We propose OpenSage, the first ADK that enables LLMs to automatically create agents with self-generated topology and toolsets while providing comprehensive and structured memory support. OpenSage offers effective functionality for agents to create and manage their own sub-agents and toolkits. It also features a hierarchical, graph-based memory system for efficient management and a specialized toolkit tailored to software engineering tasks. Extensive experiments across three state-of-the-art benchmarks with various backbone models demonstrate the advantages of OpenSage over existing ADKs. We also conduct rigorous ablation studies to demonstrate the effectiveness of our design for each component. We believe OpenSage can pave the way for the next generation of agent development, shifting the focus from human-centered to AI-centered paradigms.