Construction of a prognostic model based on cuproptosis-related genes and exploration of the value of DLAT and DLST in the metastasis for non-small cell lung cancer

Medicine (Baltimore). 2024 Dec 6;103(49):e40727. doi: 10.1097/MD.0000000000040727.

Abstract

Background: To reveal the clinical value of cuproptosis-related genes on prognosis and metastasis in non-small cell lung cancer.

Methods: Gene expression profiles and clinical information of non-small cell lung cancer were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. The data were grouped into training set, internal testing set, and external testing set. A risk prognostic model was constructed by Lasso-Cox regression analysis. Hub genes were identified and evaluated using immunohistochemistry and the transwell migration assay in 50 clinical patients.

Results: A total of 17/19 cuproptosis-related genes were differentially expressed in tumors, 8 were significantly associated with prognosis, and 4 were markedly associated with metastasis. A risk model based on 2 cuproptosis-related genes was constructed and validated for predicting overall survival. The risk score was proven to be an independent risk factor for the prognosis of non-small cell lung cancer. Dihydrolipoamide S-acetyltransferase and dihydrolipoamide S-succinyltransferase, key genes in cuproptosis, were proven to be associated with non-small cell lung cancer prognosis and metastasis. Immunohistochemistry showed that their expression significantly predicted metastasis but failed to predict prognosis in non-small cell lung cancer patients. The transwell migration assay further increased the cellular reliability of our findings.

Conclusion: The cuproptosis-related genes prognostic model effectively predicted the prognosis of non-small cell lung cancer. Dihydrolipoamide S-acetyltransferase and dihydrolipoamide S-succinyltransferase may serve as predictive markers for metastasis in non-small cell lung cancer.

MeSH terms

  • Acetyltransferases / genetics
  • Aged
  • Biomarkers, Tumor / genetics
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis / genetics
  • Prognosis
  • Risk Factors

Substances

  • Biomarkers, Tumor
  • Acetyltransferases