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Related Experiment Video

Updated: Jun 29, 2025

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Comprehensive molecular classification predicted microenvironment profiles and therapy response for HCC.

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  • 1Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

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Summary

Tumor microenvironment (TME) heterogeneity in hepatocellular carcinoma (HCC) impacts patient outcomes. This study defines 5 molecular subtypes of HCC TME, guiding personalized treatment strategies for improved precision medicine.

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Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Tumor microenvironment (TME) heterogeneity in hepatocellular carcinoma (HCC) complicates prognosis and treatment response.
  • Existing molecular subtypes of HCC TME have limited clinical applicability.

Purpose of the Study:

  • To comprehensively characterize the TME landscape in HCC using single-cell data.
  • To identify and validate novel molecular subtypes of HCC TME.
  • To explore the predictive value of these subtypes for patient prognosis and therapeutic response.

Main Methods:

  • Integration of three single-cell datasets to define TME landscape.
  • Unsupervised clustering of subcluster-specific markers to generate transcriptomic subtypes.
  • Validation of subtypes in external HCC cohorts and a clinical cohort.
  • Analysis of TME features via immune repertoire sequencing, mass cytometry, and multiplex immunofluorescence.
  • Construction of a prognosis-related score using a machine-learning algorithm.

Main Results:

  • Identification of 6 prognosis-related cell subclusters and 5 distinct transcriptomic subtypes of HCC TME.
  • Subtypes exhibit varied clinical prognoses, stemness, immune infiltration, and therapeutic responses.
  • Class 1 shows an inflamed phenotype with better outcomes; Classes 2 and 4 lack T-cell infiltration.
  • Classes 5 and 3 indicate an inhibitory TME, sensitive to immunotherapy and targeted therapy.
  • Classes 1 and 2 respond to transcatheter arterial chemoembolization; Class 4 is resistant to therapies.
  • Identification of potential therapeutic agents and targets for high-risk patients.

Conclusions:

  • Development of a clinically relevant molecular classification for HCC TME.
  • This classification enables precision medicine approaches for HCC treatment guiding.
  • The identified subtypes offer insights into differential treatment responses and prognosis.