A study on the role of cuproptosis-related immune checkpoint genes in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a common malignancy. Studies have demonstrated the crucial role of cuproptosis and immune checkpoint genes (ICGs) in the process of cancer progression, while it remains unclear whether cuproptosis-related immune checkpoint genes (CRICGs) can help predict the prognosis of NSCLC and provide guidance for establishing appropriate treatment. Thirteen cuproptosis-related genes and 79 ICGs were obtained for correlation analyses to determine the expression levels of CRICGs. Univariate Cox and least absolute shrinkage and selection operator regression analyses were conducted to identify prognosis-related CRICGs and develop a predictive model for the prognosis of NSCLC. Four CRICGs were selected to construct the predictive model, followed by an assessment of its performance. The risk score of the predictive model was deemed to be an independent prognostic factor in NSCLC. Gene set enrichment analyses showed that CRICGs were enriched in cancer-related pathways. The prognostic nomogram based on the risk scores and clinical data of NSCLC patients could accurately predict 3- and 5-year survival. The high- and low-risk groups showed significant differences in immune cell infiltration and ICG expression levels. The results of drug susceptibility testing of NSCLC to conventional targeted therapy and chemotherapy suggested a higher probability of drug resistance in the high-risk group. Finally, 8 CRICG-targeting small-molecule drugs were found to have therapeutic potential for NSCLC.