Normal view
-
cs.AI, q-bio.NC updates on arXiv.org
-
From Model Choice to Model Belief: Establishing a New Measure for LLM-Based Research
arXiv:2512.23184v1 Announce Type: new Abstract: Large language models (LLMs) are increasingly used to simulate human behavior, but common practices to use LLM-generated data are inefficient. Treating an LLM's output ("model choice") as a single data point underutilizes the information inherent to the probabilistic nature of LLMs. This paper introduces and formalizes "model belief," a measure derived from an LLM's token-level probabilities that captures the model's belief distribution over choic
-
Omics in Hepatocellular
-
Integrated Multi-Omics Profiling Identifies PDZ-Binding Kinase (PBK) as a Novel Prognostic Biomarker in Hepatocellular Carcinoma
J Hepatocell Carcinoma. 2025 Jul 17;12:1453-1469. doi: 10.2147/JHC.S493907. eCollection 2025.ABSTRACTBACKGROUND: Hepatocellular carcinoma (HCC) necessitates novel immunotherapeutic targets. PBK, a cancer/testis antigen (CTA), was identified as a pivotal hub gene influencing prognosis, tumor mutation burden (TMB), and immune microenvironment remodeling.METHODS: PBK was prioritized using weighted gene co-expression network analysis (WGCNA) and differential expression screening in the TCGA-LIHC coh
Integrated Multi-Omics Profiling Identifies PDZ-Binding Kinase (PBK) as a Novel Prognostic Biomarker in Hepatocellular Carcinoma
J Hepatocell Carcinoma. 2025 Jul 17;12:1453-1469. doi: 10.2147/JHC.S493907. eCollection 2025.
ABSTRACT
BACKGROUND: Hepatocellular carcinoma (HCC) necessitates novel immunotherapeutic targets. PBK, a cancer/testis antigen (CTA), was identified as a pivotal hub gene influencing prognosis, tumor mutation burden (TMB), and immune microenvironment remodeling.
METHODS: PBK was prioritized using weighted gene co-expression network analysis (WGCNA) and differential expression screening in the TCGA-LIHC cohort, intersected with curated CTAs. Analyses assessed correlations with clinicopathological features (TNM stage, survival), genomic characterization (mutation frequencies), and functional validation via siRNA-mediated PBK knockdown in Huh7 cells (migration assay). Single-cell RNA sequencing (scRNA-seq) profiled of the tumor immune microenvironment.
RESULTS: PBK overexpression was significantly correlated with advanced TNM stage (P < 0.05) and poor survival (log-rank P = 0.003). Genomic analysis revealed distinct mutation profiles: high-PBK tumors exhibited increased TP53 mutation frequency (39% vs 17%) but decreased CTNNB1 mutations (20% vs 31%). Patients exhibiting with combined PBK overexpression and high TMB demonstrated the poorest prognosis. Functional validation confirmed that PBK knockdown significantly inhibited Huh7 cell migration capacity (P < 0.05). scRNA-seq analysis showed PBK-enriched tumors contained elevated proportions of immunosuppressive SPP1(+) macrophages (22.33% vs 6.6%, FDR corrected P < 0.001) and CD8(+) SLC4A10(+) MAIT cells (9.82% vs 4.7%, FDR corrected P < 0.001).
CONCLUSION: PBK synergistically drives HCC progression through three synergistic mechanisms: (1) promoting oncogenic mutation accumulation (eg, TP53), (2) increasing metastatic potential, and (3) reprogramming an immune-suppressive microenvironment enriched for SPP1(+) macrophages and CD8(+)SLC4A10(+) MAIT cells. This establishes PBK as a dual-purpose biomarker for prognostic stratification and immunotherapy resistance prediction, providing a mechanistic rationale for developing PBK-targeted therapies in HCC.
PMID:40697330 | PMC:PMC12279550 | DOI:10.2147/JHC.S493907
-
Cell Death Discovery nature.com science feeds
-
Correction: Proof-of-principle studies on a strategy to enhance nucleotide imbalance specifically in cancer cells
Cell Death Discovery, Published online: 30 November 2022; doi:10.1038/s41420-022-01275-zCorrection: Proof-of-principle studies on a strategy to enhance nucleotide imbalance specifically in cancer cells
Correction: Proof-of-principle studies on a strategy to enhance nucleotide imbalance specifically in cancer cells
Cell Death Discovery, Published online: 30 November 2022; doi:10.1038/s41420-022-01275-z
Correction: Proof-of-principle studies on a strategy to enhance nucleotide imbalance specifically in cancer cells