Cuproptosis-related gene signature correlates with the tumor immune features and predicts the prognosis of early-stage lung adenocarcinoma patients

Abstract

Background: Although a majority of early-stage lung adenocarcinoma (es-LUAD) patients have a favorable prognosis, there are still some cases with a risk of recurrence and metastasis. Cuproptosis is a new form of death that differs from other programmed cell death. However, no study has been reported for setting a prognostic model of es-LUAD using cuproptosis pattern-related genes. Methods: Using multiple R packages, the data from the GEO database was processed, and es-LUAD patients was classified into two patterns based on cuproptosis-related genes. Key differentially expressed genes (DEGs) in the two patterns were screened to construct a prognostic signature to assess differences in biological processes and immunotherapy responses in es-LUAD. Tumor microenvironment (TME) in es-LUAD was analyzed using algorithms such as TIMER and ssGSEA. Then, a more accurate nomogram was constructed by combining risk scores with clinical factors. Results: Functional enrichment analysis revealed that DEGs in two patterns were correlated with organelle fission, nuclear division, chromosome segregation, and cycle-related pathways. Univariate Cox regression and Lasso-Cox regression analyses identified six prognostic genes: ASPM, CCNB2, CDC45, CHEK1, NCAPG, and SPAG5. Based on the constructed model, we found that the high-risk group patients had higher expression of immune checkpoints (CTLA4, LAG3, PD-L1, TIGIT and TIM3), and a lower abundance of immune cells. Lastly, the nomogram was highly accurate in predicting the 1-, 3-, and 5-year survival status of patients with es-LUAD based on risk scores and clinical factors. Conclusion: The cuproptosis pattern-related signature can serve as a potential marker for clinical decision-making. It has huge potential in the future to guide the frequency of follow-up and adjuvant therapy for es-LUAD patients.