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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631004PMC
http://dx.doi.org/10.1097/MD.0000000000040727DOI Listing

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