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Multi-Omics Biomarker Signatures for Precision Diagnosis and Prognosis in Primary Liver Cancer: A Literature Review
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
CAFs shape the immunosuppressive microenvironment of pancreatic cancer through the Lin28b-STING Axis
Nat Commun. 2026 Aug 7;17(1):9491. doi: 10.1038/s41467-026-76495-3.
ABSTRACT
Cancer-associated fibroblasts comprise diverse functionally distinct cellular subsets, with certain subpopulations exerting pivotal influence in shaping the pancreatic cancer immune microenvironment. Here we show that Lin28b+ cancer-associated fibroblasts contribute to establishing an immunologically cold tumor microenvironment in pancreatic ductal adenocarcinoma. Mechanistically, Lin28b directly binds to STING mRNA and promotes its degradation, thereby suppressing STING expression and downstream type I interferon signaling. Loss of Lin28b in cancer-associated fibroblasts activates the cGAS-STING-interferon signaling cascade, enhancing dendritic cell antigen presentation and CD8+ T cell cytotoxic function. Importantly, genetic inhibition of Lin28b in cancer-associated fibroblasts enhances sensitivity to anti-PD-L1 immune checkpoint blockade therapy. These findings reveal that targeting the Lin28b-STING axis represents a promising therapeutic strategy for overcoming the intrinsic resistance of pancreatic ductal adenocarcinoma to immunotherapy.
PMID:42693143 | PMC:PMC13542369 | DOI:10.1038/s41467-026-76495-3
Disruption of the AR/ZNF217/PROM2 axis sensitizes prostate cancer to ferroptosis and enzalutamide therapy
Oncogenesis, Published online: 11 August 2026; doi:10.1038/s41389-026-00649-7
Disruption of the AR/ZNF217/PROM2 axis sensitizes prostate cancer to ferroptosis and enzalutamide therapyHyperGuide: Hyperbolic Guidance for Efficient Multi-Step Reasoning in Large Language Models
PHGNet: Prototype-Guided Hypergraph Construction for Heterogeneous Spatiotemporal Forecasting
STREAM: A Data-Centric Framework for Mining High-Value Task-Oriented Dialogues from Streaming Media
Reliable AI Needs to Externalize Implicit Knowledge: A Human-AI Collaboration Perspective
SURGE: Surrogate Gradient Adaptation in Binary Neural Networks
Personalized neoadjuvant treatment regimen selection in locally advanced rectal cancer based on regimen-specific response modeling
npj Digital Medicine, Published online: 26 May 2026; doi:10.1038/s41746-026-02798-w
Personalized neoadjuvant treatment regimen selection in locally advanced rectal cancer based on regimen-specific response modelingHuman pancreatic progenitor organoids define genetic and epigenetic barriers to early PDAC transformation
Dev Cell. 2026 May 19:S1534-5807(26)00159-0. doi: 10.1016/j.devcel.2026.04.012. Online ahead of print.
ABSTRACT
The lack of accurate human models that recapitulate pancreatic ductal adenocarcinoma (PDAC) initiation has hindered therapeutic development. Using pluripotent stem cell-derived pancreatic progenitor organoids, we established a human PDAC model that faithfully reproduces the genetic, epigenetic, and transcriptomic trajectories of tumor initiation and progression, validated against clinical datasets and tumor histopathology. We demonstrate that CDKN2A loss, which is nearly universal in patients but dispensable in mouse models, is essential for neoplastic transformation when combined with KRAS and TP53 mutations, whereas SMAD4 loss promotes tumor progression. Multi-omics profiling reveals epigenetic repression of the pancreatic lineage program during PDAC initiation, alongside AP-1-driven chromatin remodeling. We identify TET1 suppression as a mechanistic link between oncogenic ERK signaling and hypermethylation of essential pancreatic transcription factors. This model captures genetic and epigenetic determinants of human PDAC, reveals antagonism between oncogenic and lineage restriction programs, and supports TET-based lineage restoration as a potential early intervention strategy.
PMID:42161274 | PMC:PMC13196429 | DOI:10.1016/j.devcel.2026.04.012
Advancing solar and wind penetration in China through energy complementarity
Nature, Published online: 20 May 2026; doi:10.1038/s41586-026-10570-z
Using high-resolution satellite imagery combined with a deep-learning-based framework to build a national energy inventory enables a data-driven assessment of solar–wind complementarity strategies to reduce power variability and enhance renewable energy penetration across China.GPNMB Drives Brain Metastasis by Sculpting a Pathological Endothelial-Immune Interactome
Cancer Discov. 2026 Apr 15. doi: 10.1158/2159-8290.CD-25-1663. Online ahead of print.
ABSTRACT
Brain metastases (BM) remain a devastating disease with dismal prognosis. How circulating tumor cells (CTCs) penetrate the blood brain barrier (BBB) and reprogram the brain microenvironment remain unclear. Using spatially resolved multi-omic profiling of CTCs and brain metastases, integrated with experimental and clinical analyses, we identified Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB) as a CTC-secreted driver of vascular disruption and brain colonization. CBX3 upregulation induced GPNMB expression, which bound endothelial EGFR, triggering CBL-mediated ubiquitination and degradation. Attenuated EGFR signaling suppressed FTO and disrupted endothelial junctions via YTHDF2-dependent TJP1 m6A methylation. Remarkably, GPNMB-induced BBB remodeling promoted immune infiltration via CXCL12-CXCR4 axis, and induced time course-dependent T cell exhaustion within the brain microenvironment. Clinically, elevated CBX3⁺GPNMB⁺ CTCs and plasma CXCL12 were significantly associated with BM progression in lung cancer and melanoma. Therapeutically, dual blockade of GPNMB and PD1 enhanced anti-BM efficacy in mice, unveiling GPNMB as a promising target for precision immunotherapy.
PMID:41973996 | DOI:10.1158/2159-8290.CD-25-1663
Pan-neurodegeneration proteomics reveals disease subtypes and molecular signatures
A Genetically Engineered Human Organoid Model Reveals Distinct Genetic and Epigenetic Barriers of Lineage Plasticity in Early PDAC Transformation
bioRxiv [Preprint]. 2026 Mar 11:2026.03.09.710586. doi: 10.64898/2026.03.09.710586.
ABSTRACT
The lack of accurate, human-based models recapitulating early-stage pancreatic ductal adenocarcinoma (PDAC) has hindered therapeutic development. Using pluripotent stem cell-derived pancreatic progenitor organoids, we established a human PDAC model that faithfully reproduces the genetic, epigenetic, and transcriptomic trajectory of tumor initiation and progression in vitro , validated against clinical datasets and histopathology. We demonstrate that CDKN2A loss, nearly universal in patients but dispensable in mouse models, is essential for neoplastic transformation when combined with KRAS and TP53 mutations, while SMAD4 loss promotes tumor progression. Multi-omics profiling reveals epigenetic repression of pancreatic lineage program during PDAC initiation, alongside oncogenic AP-1-driven chromatin remodeling. Notably, we identify TET1 suppression as a mechanistic link between oncogenic ERK signaling and the hypermethylation and silencing of essential pancreatic transcription factors. This model captures the genetic and epigenetic determinants of human PDAC, reveals antagonism between oncogenic and lineage restriction programs, and supports TET-based lineage restoration as a promising early intervention strategy for high-risk individuals.
PMID:41959451 | PMC:PMC13060829 | DOI:10.64898/2026.03.09.710586
The importance of competition and facilitation for global tree diversity
Nature, Published online: 08 April 2026; doi:10.1038/s41586-026-10349-2
Across 17 forest plots (2.7 million trees, 5,400 species), competition dominated overall, but facilitation was relatively stronger near the equator and declined towards higher latitudes, partly linked to temperature, legumes, mycorrhizal associations and canopy nursing effect.