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

Nat Commun. 2026 Mar 20;17(1):2655. doi: 10.1038/s41467-026-70193-w.

ABSTRACT

Pulmonary fibrosis represents a progressive interstitial lung disease marked by excessive extracellular matrix deposition and architectural distortion. Vascular endothelial cells critically contribute to fibrogenesis through paracrine secretion of pro-fibrotic mediators, yet their mechanobiological regulation remains elusive. Using integrated single-cell multi-omics profiling of human pulmonary fibrosis specimens and experimental fibrosis models induced by bleomycin or silica, we identify mechanosensitive Piezo1 upregulation in Endothelial cells as a hallmark of fibrotic progression. Endothelial-specific Piezo1 knockout significantly attenuates Bleomycin-induced fibrotic remodeling in male mice, establishing its pathogenic necessity. Mechanistically, PIEZO1 activation promotes pulmonary fibrosis development via CAPN2-mediated STAT3 phosphorylation, which may regulate the secretion of the pro-fibrotic molecule interleukin-33. These findings suggest that the endothelial PIEZO1-CAPN2-STAT3-IL33 axis is a potential therapeutic target for PF intervention.

PMID:41862476 | PMC:PMC13004862 | DOI:10.1038/s41467-026-70193-w