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Multi-Omics Biomarker Signatures for Precision Diagnosis and Prognosis in Primary Liver Cancer: A Literature Review

4 September 2026 at 18:00

Biofactors. 2026 Sep-Oct;52(5):e70136. doi: 10.1002/biof.70136.

ABSTRACT

Primary liver cancer (PLC) is a biologically heterogeneous group of malignancies dominated by hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and a smaller subset of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), and its clinical burden remains high because current diagnostic and prognostic tools do not adequately capture molecular diversity. Conventional imaging, serum markers, and histopathological assessment remain insufficient for precise early diagnosis, subtype-resolved classification, and outcome stratification, while tissue and liquid biopsy approaches have expanded the range of analytes available for clinical assessment. Recent studies have identified candidate biomarker signatures across genomic, epigenomic, transcriptomic, proteomic, metabolomic, and circulating layers, suggesting that integrated multi-omics profiling may better represent tumor lineage, clonal evolution, immune context, and therapeutic vulnerability than isolated molecular readouts. However, these layers are not equally mature for clinical use: genomic testing is closest to routine therapeutic application in iCCA, plasma methylation assays are advancing for HCC surveillance augmentation, and many proteomic or metabolomic panels remain validation-stage tools. Their clinical value remains constrained by sampling bias, biospecimen-dependent signal loss, assay standardization, cost, and the need for prospective validation across clinically diverse populations. This narrative review critically synthesizes current evidence on multi-omics biomarker signatures for precision diagnosis and prognosis in primary liver cancer and argues that clinically useful signatures should be question-specific, stage-aware, and specimen-aware rather than universal multi-analyte panels.

PMID:42697859 | PMC:PMC13545153 | DOI:10.1002/biof.70136

Cuproptosis causes meiotic metaphase I arrest by disrupting mitochondrial functions in oocytes

Cell Death Discovery, Published online: 23 May 2026; doi:10.1038/s41420-026-03168-x

Cuproptosis causes meiotic metaphase I arrest by disrupting mitochondrial functions in oocytes

From Concept to Practice: an Automated LLM-aided UVM Machine for RTL Verification

arXiv:2504.19959v4 Announce Type: cross Abstract: Verification presents a major bottleneck in Integrated Circuit (IC) development, consuming nearly 70% of the total development effort. While the Universal Verification Methodology (UVM) is widely used in industry to improve verification efficiency through structured and reusable testbenches, constructing these testbenches and generating sufficient stimuli remain challenging. These challenges arise from the considerable manual coding effort required, repetitive manual execution of multiple EDA tools, and the need for in-depth domain expertise to navigate complex designs.Here, we present UVM^2, an automated verification framework that leverages Large Language Models (LLMs) to generate UVM testbenches and iteratively refine them using coverage feedback, significantly reducing manual effort while maintaining rigorous verification standards.To evaluate UVM^2, we introduce a benchmark suite comprising Register Transfer Level (RTL) designs of up to 1.6K lines of code.The results show that UVM^2 reduces testbench setup time by up to UVM^2 compared to experienced engineers, and achieve average code and function coverage of 87.44% and 89.58%, outperforming state-of-the-art solutions by 20.96% and 23.51%, respectively.

Open3DBench: Open-Source Benchmark for 3D-IC Backend Implementation and PPA Evaluation

arXiv:2503.12946v2 Announce Type: replace-cross Abstract: This work introduces Open3DBench, an open-source 3D-IC backend implementation benchmark built upon the OpenROAD-flow-scripts framework, enabling comprehensive evaluation of power, performance, area, and thermal metrics. Our proposed flow supports modular integration of 3D partitioning, placement, 3D routing, RC extraction, and thermal simulation, aligning with advanced 3D flows that rely on commercial tools and in-house scripts. We present two foundational 3D placement algorithms: Open3D-Tiling, which emphasizes regular macro placement, and Open3D-DMP, which enhances wirelength optimization through cross-die co-placement with analytical placer DREAMPlace. Experimental results show significant improvements in area (51.19%), wirelength (24.06%), timing (30.84%), and power (5.72%) compared to 2D flows. The results also highlight that better wirelength does not necessarily lead to PPA gain, emphasizing the need of developing PPA-driven methods. Open3DBench offers a standardized, reproducible platform for evaluating 3D EDA methods, effectively bridging the gap between open-source tools and commercial solutions in 3D-IC design.

Chain-of-Authorization: Internalizing Authorization into Large Language Models via Reasoning Trajectories

arXiv:2603.22869v1 Announce Type: new Abstract: Large Language Models (LLMs) have become core cognitive components in modern artificial intelligence (AI) systems, combining internal knowledge with external context to perform complex tasks. However, LLMs typically treat all accessible data indiscriminately, lacking inherent awareness of knowledge ownership and access boundaries. This deficiency heightens risks of sensitive data leakage and adversarial manipulation, potentially enabling unauthorized system access and severe security crises. Existing protection strategies rely on rigid, uniform defense that prevent dynamic authorization. Structural isolation methods faces scalability bottlenecks, while prompt guidance methods struggle with fine-grained permissions distinctions. Here, we propose the Chain-of-Authorization (CoA) framework, a secure training and reasoning paradigm that internalizes authorization logic into LLMs' core capabilities. Unlike passive external defneses, CoA restructures the model's information flow: it embeds permission context at input and requires generating explicit authorization reasoning trajectory that includes resource review, identity resolution, and decision-making stages before final response. Through supervised fine-tuning on data covering various authorization status, CoA integrates policy execution with task responses, making authorization a causal prerequisite for substantive responses. Extensive evaluations show that CoA not only maintains comparable utility in authorized scenarios but also overcomes the cognitive confusion when permissions mismatches. It exhibits high rejection rates against various unauthorized and adversarial access. This mechanism leverages LLMs' reasoning capability to perform dynamic authorization, using natural language understanding as a proactive security mechanism for deploying reliable LLMs in modern AI systems.

Advancing Automated Algorithm Design via Evolutionary Stagewise Design with LLMs

arXiv:2603.07970v1 Announce Type: new Abstract: With the rapid advancement of human science and technology, problems in industrial scenarios are becoming increasingly challenging, bringing significant challenges to traditional algorithm design. Automated algorithm design with LLMs emerges as a promising solution, but the currently adopted black-box modeling deprives LLMs of any awareness of the intrinsic mechanism of the target problem, leading to hallucinated designs. In this paper, we introduce Evolutionary Stagewise Algorithm Design (EvoStage), a novel evolutionary paradigm that bridges the gap between the rigorous demands of industrial-scale algorithm design and the LLM-based algorithm design methods. Drawing inspiration from CoT, EvoStage decomposes the algorithm design process into sequential, manageable stages and integrates real-time intermediate feedback to iteratively refine algorithm design directions. To further reduce the algorithm design space and avoid falling into local optima, we introduce a multi-agent system and a "global-local perspective" mechanism. We apply EvoStage to the design of two types of common optimizers: designing parameter configuration schedules of the Adam optimizer for chip placement, and designing acquisition functions of Bayesian optimization for black-box optimization. Experimental results across open-source benchmarks demonstrate that EvoStage outperforms human-expert designs and existing LLM-based methods within only a couple of evolution steps, even achieving the historically state-of-the-art half-perimeter wire-length results on every tested chip case. Furthermore, when deployed on a commercial-grade 3D chip placement tool, EvoStage significantly surpasses the original performance metrics, achieving record-breaking efficiency. We hope EvoStage can significantly advance automated algorithm design in the real world, helping elevate human productivity.
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