Evidence map›Paper›PMID 41792761›Full record

ArticleMolecular cancer2026

Multi-omics profiling reveals divergent biology and liver microenvironment in HCC of metastatic and de novo origin.

Gina F Boot, Fabian Haak, Mairene Coto-Llerena, Tuyana Boldanova, Eva Dazert, Philip Sedlaczek, George Rosenberger, Cinzia Esposito, Caner Ercan, Stefan Wieland and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Gina F BootDepartment of Biomedicine, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-2463-6412
Fabian HaakUniversity Digestive Health Care Center Basel - Clarunis, Basel, Switzerland.ORCID http://orcid.org/0000-0002-0279-1745
Mairene Coto-LlerenaDepartment of Biomedicine, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0001-7596-1250
Tuyana BoldanovaDepartment of Biomedicine, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0009-0005-2745-0057
Eva DazertBiozentrum, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-7292-2261
Philip SedlaczekUniversity Digestive Health Care Center Basel - Clarunis, Basel, Switzerland.ORCID http://orcid.org/0000-0002-7310-7103
George RosenbergerBiozentrum, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-1655-6789
Cinzia EspositoDepartment of Biomedicine, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0009-0007-8211-0885
Caner ErcanInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-5611-2699
Stefan WielandDepartment of Biomedicine, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-4444-977X
Salvatore Lorenzo RenneDepartment of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.ORCID http://orcid.org/0000-0002-0186-1318
Andrej BenjakDepartment for BioMedical Research (DBMR), University of Bern, Bern, Switzerland.ORCID http://orcid.org/0000-0003-4522-6575
Matthias S MatterInstitute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-2005-5266
Luca Di TommasoDepartment of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.ORCID http://orcid.org/0000-0002-9013-4728
Michael N HallBiozentrum, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-2998-0757
Luigi M TerraccianoDepartment of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.ORCID http://orcid.org/0000-0002-9393-9660
Markus H HeimDepartment of Biomedicine, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-7523-4894
Salvatore Piscuoglio *Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy.ORCID http://orcid.org/0000-0003-2686-2939
Charlotte K Y Ng *Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, Pieve Emanuele, 20072, Milan, Italy. charlotte.ng@hunimed.eu.ORCID http://orcid.org/0000-0002-6100-0026

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMultifocal hepatocellular carcinoma (mfHCC) arises via intrahepatic metastasis (IM) or multicentric occurrence (MO), each with distinct biological behavior and clinical implications, though mfHCC origin is rarely assessed in clinical practice. We aimed to characterize the clinicopathological and molecular features of IM-HCC, MO-HCC, and their surrounding non-tumor liver (NTL) tissues using multi-omics analyses.

methodsWe analyzed 76 tumor and 44 NTL biopsies from 22 patients, using whole-exome sequencing, RNA-sequencing, and proteomic/phosphoproteomic profiling. Patients were classified as IM, MO or mixed (IM + MO) according to their somatic mutations. A comparator cohort of 48 unifocal HCC and 15 normal livers was used. Clinicopathological parameters, pathway and transcription factor activities, immune infiltration, and targetable alterations were assessed.

resultsClonality analysis identified 10 IM, 9 MO, and 3 mixed patients. IM-HCCs showed more frequent macrovascular invasion and extrahepatic metastases, with upregulation of E2F/MYC-related cell cycle pathways, higher expression of metastasis-associated genes (e.g., TTK, BUB1, NUF2), higher CD8 + T-cell exhaustion, and shared actionable mutations (e.g. PTEN). MO-HCCs within patients displayed molecular dissimilarity comparable to tumors from different patients, though they also showed convergent kinase and pathway dysregulation. NTLs of IM-HCC patients had lower fibrosis, extracellular matrix signaling and pro-regenerative pathways (e.g., SOX2, TGFA) than those of MO-HCC.

conclusionsThe aggressive molecular features and immune exhaustion of IM-HCC support the need for combined therapies, while the convergence of kinase and pathway dysregulation of MO-HCC provides unified therapeutic opportunities. Key differences in fibrogenic and regenerative pathways may influence metastatic potential. Our findings provide insights into the biological behavior and therapeutic opportunities in mfHCC.

Indexed as

Carcinoma, HepatocellularGenomicsLiver NeoplasmsTumor MicroenvironmentAgedBiomarkers, TumorExome SequencingFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleMiddle AgedMultiomicsMutationNeoplasm MetastasisBiomarkers, TumorHepatocellular carcinomaIntrahepatic metastasisMulticentric occurrenceMultiomics profilingProteomics

Identifiers

PMID41792761
PMCPMC13078022

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.