A Novel Cuproptosis-Related Gene Signature Predicts Prognosis in Papillary Thyroid Carcinoma Patients

Abstract

background: Cuproptosis is a novel type of cell death mediated by protein lipoylation，and is closely related to mitochondrial metabolism. Clinical association of cuproptosis-related genes（CRGs）in thyroid cancer, however, remains unclear. In this study, we systematically evaluated the differential expression and genetic alterations of CRGs in papillary thyroid cancer (PTC) and constructed a CRG signature to predict the prognosis of PTC patients. method: We integrated the data of The Cancer Genome Atlas (TCGA) database and analyzed the expression of 10 CRGs in PTC. CRG signature was constructed by univariate Cox analysis and selection operator (LASSO) Cox regression. In addition, the signature-related molecular features were validated by a combination of functional enrichment, Cox regression, and immune infiltration analysis. Independent validation cohort data and quantitative real-time polymerase chain reaction (qRT-PCR) were used to validate the expression of differentially expressed CRG (CDKN2A). result: Thyroid cancer patients could be divided into two subtypes (low and high CRG score groups) and we found that overall survival (OS) of patients was lower in high CRG score group (HCSG) than in low CRG score group (LCSG) (p < 0.001). And the area under the curve (AUC) values for 3 years, 5 years, and 8 years were 0.872, 0.941, and 0.976, respectively. Cox regression analysis showed that the CRG score could be used as an independent prognostic indicator for PTC. Functional enrichment analysis indicated that the CRG prognostic signature was also associated with the tumor immune microenvironment. In HCSG, the immune suppression type cell score is significantly higher than in LCSG. In addition, we identified the expression of CRG (CDKN2A) by qRT-PCR, and the results were consistent with the TCGA database. conclusion: Our CRG signature has a good predictive ability for the prognosis of PTC patients. CRGs may play an important role in tumorigenesis and could be used to predict immunotherapy efficacy of PTC.