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Non-Invasive Assessment of Microvascular Invasion Risk in Hepatocellular Carcinoma Using Liquid Biopsy: Translational Insights and Clinical Implications
Diagnostics (Basel). 2026 Aug 22;16(17):2686. doi: 10.3390/diagnostics16172686.
ABSTRACT
Microvascular invasion (MVI) is a critical prognostic indicator for recurrence and survival in hepatocellular carcinoma (HCC); however, its accurate preoperative assessment remains clinically challenging. Postoperative histopathology is subject to sampling bias and time delays, while traditional imaging techniques lack the molecular specificity required to predict MVI. Liquid biopsy, through the analysis of circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), circulating tumor RNA (ctRNA), and extracellular vesicles (EVs), provides a minimally invasive approach for capturing tumor-derived molecular and cellular signals associated with vascular invasion. This narrative review comprehensively summarizes the current evidence linking these four liquid biopsy analyte categories to MVI in HCC, evaluates their integration into multi-omics predictive models, including multi-marker, clinicopathological-integrated, and imaging-integrated strategies, and proposes an evidence-level framework that categorizes blood biomarkers according to the strength of their support for MVI prediction, distinguishing direct histopathological validation from indirect associations with aggressive tumor biology. Key challenges are critically examined, including the variable specificity of individual biomarkers for MVI, the lack of head-to-head comparative studies, the absence of standardized pre-analytical and analytical protocols, and the methodological limitations of current prediction models. As a narrative review, this work does not employ systematic review methodology, and the evidence synthesis should be interpreted accordingly. The review provides a framework for understanding how liquid biopsy-based MVI risk stratification may inform surgical and perioperative decision-making following prospective validation.
PMID:42739118 | PMC:PMC13564874 | DOI:10.3390/diagnostics16172686
Refined immune-based molecular subtypes of gastric cancer: Integrating mismatch repair status and tumor microenvironment for enhanced immunotherapy prediction
Chin J Cancer Res. 2026 Apr 30;38(2):234-251. doi: 10.21147/j.issn.1000-9604.2026.02.09.
ABSTRACT
OBJECTIVE: Gastric cancer (GC) is heterogeneous, and current mismatch repair (MMR)-based classifications incompletely predict response to immune checkpoint inhibitors (ICIs).
METHODS: RNA sequencing (RNA-seq) and immune infiltration profiles from 189 resected GC were used to derive four refined immune-MMR subtypes (R1-R4) by integrating MMR status, survival, and tumor microenvironment (TME) features. Multi-omics profiling and pathway analysis defined subtype biology. External transcriptomic cohorts and an ICI-treated cohort were classified with Nearest Template Prediction (NTP). Immune response-associated genes were identified from responder vs. non-responder comparisons within the ICI-sensitive subtype and validated by multiplex immunohistochemistry (mIHC).
RESULTS: R1 showed the best prognosis and highest immunotherapy response with objective response rate (ORR) 54.5%, while R4 had the worst prognosis. R2 represented an immune-unresponsive deficient mismatch repair (dMMR) subset, and R3 captured an immune-active proficient mismatch repair (pMMR) subgroup with moderate therapy sensitivity. Multi-omics integration revealed subtype-specific pathways (e.g., ECM remodeling in R1, metabolic reprogramming in R2). Reclassification of pMMR tumors based on transcriptional similarity to R1 identified a New R3 subset with enhanced immune features and higher ICI response. Eight immune response-associated genes (e.g., CXCL10, CXCL11, ELN, GAD1, IL32, MT1E, OR2I1P, SLC3A1) were identified and validated by mIHC for predictive relevance.
CONCLUSIONS: This immune-based molecular framework refines risk stratification beyond conventional MMR categories, identifies ICI-sensitive subsets among both dMMR and pMMR tumors, and proposes candidate biomarkers for patient selection.
PMID:42147371 | PMC:PMC13171420 | DOI:10.21147/j.issn.1000-9604.2026.02.09
Open3DBench: Open-Source Benchmark for 3D-IC Backend Implementation and PPA Evaluation
Heracles: Bridging Precise Tracking and Generative Synthesis for General Humanoid Control
Dual function of DOT1L suppresses tumor cell-intrinsic immunogenicity in hepatocellular carcinoma
Oncogene, Published online: 31 March 2026; doi:10.1038/s41388-026-03744-6
Dual function of DOT1L suppresses tumor cell-intrinsic immunogenicity in hepatocellular carcinoma