Identification of ACAA1 and HADHB as potential prognostic biomarkers based on a novel fatty acid oxidation-related gene model in head and neck squamous cell carcinoma: A retrospective study

Arch Oral Biol. 2024 Jul:163:105982. doi: 10.1016/j.archoralbio.2024.105982. Epub 2024 Apr 24.

Abstract

Objectives: To investigate the importance of fatty acid oxidation (FAO)-related genes in predicting the progression and prognosis of head and neck squamous cell carcinoma (HNSCC).

Methods: The FAO-related gene prognostic model was established employing Cox regression analyses, during which accuracy and sensitivity of the gene model were evaluated in The Cancer Genome Atlas (TCGA) internal testing and Gene Expression Omnibus (GEO) external validation cohorts. Ultimately, hub genes were identified among 13 model genes using STRING and Cytoscape, with preliminary validation carried out through immunohistochemistry.

Results: The model, which comprised 13 genes (ABCD2, ACAA1, ACACB, AKT1, CNR1, CPT1C, CROT, ECHDC2, ETFA, HADHB, IRS2, LONP2, and SLC25A17), was established. On the basis of the median risk score, the two cohorts were grouped into low-and high-risk groups in the subsequent test and validation, and the former exhibited significantly higher survival rates than the latter. Nomograms were established based on prognostic factors, including stage and risk score, and individualized for the prediction of HNSCC patients. Ultimately, immunohistochemical staining showed that ACAA1 and HADHB were significantly under-expressed in HNSCC, with a favorable prognosis associated with low HADHB and high ACAA1.

Conclusions: The gene prognostic model has illustrated promising capability in predicting the prognosis, and ACAA1 and HADHB might serve as potential therapeutic biomarkers for HNSCC patients.

Keywords: Fatty acid oxidation; Gene prognostic model; Head and neck squamous cell carcinoma; Immunohistochemical staining.

MeSH terms

  • Aged
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Fatty Acids* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Head and Neck Neoplasms* / genetics
  • Head and Neck Neoplasms* / metabolism
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Nomograms*
  • Oxidation-Reduction
  • Prognosis
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / metabolism
  • Squamous Cell Carcinoma of Head and Neck* / pathology

Substances

  • Biomarkers, Tumor
  • Fatty Acids