PANoptosis-related molecule CASP2 affects the immune microenvironment and immunotherapy response of hepatocellular

Yichao Lou1, Desheng Chen1, Qi Gu1

  • 1Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Heliyon
|March 21, 2024
PubMed
Abstract

Insights

This study reveals that Caspase-2 (CASP2), a PANoptosis-related molecule, is linked to poor prognosis in hepatocellular carcinoma (HCC). CASP2 influences the tumor microenvironment, immunotherapy response, and drug sensitivity, offering new therapeutic directions.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • The role of PANoptosis-related molecules in hepatocellular carcinoma (HCC) remains largely uncharacterized.
  • Understanding these molecular players is crucial for developing novel therapeutic strategies against HCC.

Purpose of the Study:

  • To comprehensively investigate the involvement of PANoptosis-related genes in HCC.
  • To identify and analyze the specific role of Caspase-2 (CASP2) in HCC progression and patient outcomes.

Main Methods:

  • Utilized R packages for data analysis of publicly available datasets from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC).
  • Performed comprehensive bioinformatic analyses, including pathway enrichment, immune microenvironment assessment, drug sensitivity analysis, and single-cell distribution analysis of CASP2.
  • Constructed a prognostic model based on CASP2-derived molecules and validated findings through in vitro experiments.

Main Results:

  • Caspase-2 (CASP2) was identified as a key molecule associated with poor prognosis and adverse clinical features in HCC patients.
  • CASP2 is implicated in multiple carcinogenic pathways, significantly alters the HCC immune microenvironment, and impacts immunotherapy response.
  • Elevated CASP2 levels correlate with differential sensitivity to specific chemotherapeutic agents and targeted therapies.
  • In vitro studies demonstrated that CASP2 inhibits HCC cell proliferation, invasion, and migration.

Conclusions:

  • This study elucidates the multifaceted role of the PANoptosis-related molecule CASP2 in hepatocellular carcinoma.
  • CASP2 serves as a potential prognostic biomarker and therapeutic target in HCC, influencing tumor progression and treatment response.

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