A novel cuproptosis‐related prognostic gene signature in adrenocortical carcinoma

• Published in: Journal of clinical laboratory analysis Vol. 37; no. 21-22; pp. e24981 - n/a
• Main Authors: Gao, Wenjun, He, Xiaoyan, Huangfu, Qi, Xie, Yanqi, Chen, Keliang, Sun, Chengfang, Wei, Jingchao, Wang, Bohan
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.11.2023; John Wiley and Sons Inc
• Subjects: Adrenal Cortex Neoplasms - genetics; adrenocortical carcinoma (ACC); Adrenocortical Carcinoma - genetics; Agenesis of Corpus Callosum; Apoptosis; Cancer; Carcinoma; CDKN2A; Cell death; Copper; Cuproptosis; Cyclin-dependent kinases; Databases, Factual; Datasets; Dehydrogenases; FDX1; Gene expression; Genomes; Homeostasis; Humans; Kinases; Medical prognosis; Metastases; Metastasis; Neuroendocrine tumors; Prognosis; Proteins; Regression analysis; Respiration; Risk groups; risk score; Software; Statistical analysis; Tumors; adrenocortical carcinoma (ACC); CDKN2A; Cuproptosis; FDX1; risk score
• ISSN: 0887-8013; 1098-2825
• DOI: 10.1002/jcla.24981

Background Adrenocortical carcinoma (ACC) is an aggressive and rare malignant tumor associated with poor outcomes. Cuproptosis, a new pattern of cell death, relies on mitochondrial respiration and is associated with protein lipoylation. Increasing evidence has demonstrated the potential roles of cuproptosis in several tumor entities. However, the relationship between cuproptosis and ACC remains unclear. Methods In total, 10 cuproptosis‐related genes (CRGs) of patients with ACC were obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and differential expression analysis of CRGs was analyzed. Functional enrichment of the CRGs was performed and protein–protein interaction analysis was utilized to explore the association between the CRGs. Cuproptosis‐related risk score (CRRS) was constructed by Lasso Cox regression and validated. Results In the current study, the alteration and expression patterns of 10 CRGs in TCGA–ACC datasets were analyzed. We identified different expression patterns of CRGs in ACCs, discovered strong associations between CRGs and ACCs, and found that the CRGs were associated with immune infiltration in ACCs. A CRRS was created thereafter to predict overall survival (OS). CRRS = (0.083103718) *FDX1 + (−0.278423862) *LIAS+(0.090985682) *DLAT+(−0.018784047) *PDHA1 + (0.297218951) *MTF1 + (0.310197964) *CDKN2A. Patients were divided into high‐ and low‐risk groups based on their CRRS, and independent prognostic factors were investigated. Finally, CDKN2A and FDX1 were found to be independent prognostic predictors of patients with ACC. Conclusions CDKN2A and FDX1 are independent prognostic predictors of patients with ACC. Cuproptosis may play a role in the development of ACC, providing a new perspective on therapeutic strategies related to CRGs for cancer prevention and treatment. Validation of independent prognostic factors of the cuproptosis‐related risk score (CRRS) using a survival curve and a time‐dependent ROC (A). CDKN2A and FDX1 expressions were independent prognostic predictors of ACC patients, and low expression of CDKN2A (B) and FDX1 (C) was associated with better survival outcomes.