Published online Nov 26, 2022. doi: 10.12998/wjcc.v10.i33.12089
Peer-review started: June 18, 2022
First decision: August 6, 2022
Revised: August 18, 2022
Accepted: October 9, 2022
Article in press: October 9, 2022
Published online: November 26, 2022
Esophageal cancer is one of the most common malignant tumors of the digestive system, with a 5-year survival rate of 15% to 50%. Cuproptosis, a unique kind of cell death driven by protein lipoylation, is strongly connected to mitochondrial metabolism. The clinical implications of cuproptosis-related genes in esophageal cancer, however, are mainly unknown.
To identify cuprotosis-related genes that are differentially expressed in esophageal cancer and investigate their prognostic significance.
With |log fold change| > 1 and false discovery rate < 0.05 as criteria, the Wilcox test was used to evaluate the differentially expressed genes between 151 tumor tissues and 151 normal esophageal tissues. Cuproptosis-related genes were selected to be linked with prognosis using univariate Cox regression analysis. Genes were separated into high- and low- expression groups based on their cutoff value of gene expression, and the correlation between the two groups and overall survival or progression-free survival was investigated using the log-rank test. The C-index, calibration curve, and receiver operator characteristic (ROC) curve were used to assess a nomogram containing clinicopathological characteristics and cuproptosis-related genes.
Pyruvate dehydrogenase A1 (PDHA1) was found to be highly correlated with prognosis in univariate Cox regression analysis (hazard ratio = 22.96, 95% confidence interval = 3.09-170.73; P = 0.002). According to Kaplan-Meier survival curves, low expression of PDHA1 was associated with a better prognosis (log-rank P = 0.0007). There was no significant correlation between PDHA1 expression and 22 different types of immune cells. Tumor necrosis factor superfamily member 15 (TNFSF15) (P = 3.2 × 10-6; r = 0.37), TNFRSF14 (P = 8.1 × 10-8; r = 0.42), H long terminal repeat-associating 2 (P = 6.0 × 10-8; r = 0.42) and galectin 9 (P = 3.1 × 10-6; r = 0.37) were all found to be considerably greater in the high PDHA1 expression group, according to an analysis of genes related to 47 immunological checkpoints. The low PDHA1 expression group had significantly lower levels of cluster of differentiation 44 (CD44) (P = 0.00028; R = -0.29), TNFRSF18 (P = 1.2 × 10-5; R = -0.35), programmed cell death 1 ligand 2 (P = 0.0032; R = -0.24), CD86 (P = 0.018; R = -0.19), and CD40 (P = 0.0047; R = -0.23), and the differences were statistically significant. We constructed a prognostic nomogram incorporating pathological type, tumor-node-metastasis stage, and PDHA1 expression, and the C-index, calibration curve, and ROC curve revealed that the nomogram’s predictive performance was good.
Cuproptosis-related genes can be used as a prognostic predictor for esophageal cancer patients, providing novel insights into cancer treatment.
Core Tip: Esophageal carcinoma has a poor prognosis and is one of the major causes of cancer-related deaths worldwide. Despite recent advancements in the surgical and pharmacological treatment of esophageal cancer, the prognosis remains poor. Copper toxicity has been linked to the incidence and progression of esophageal cancer in numerous studies. At the gene level, however, the probable biochemical mechanism is unknown. We included 19 cuproptosis-related genes and screened a gene that could successfully predict the prognosis of esophageal cancer by statistical analysis to further elucidate the role of cuproptosis-related genes in impacting the prognosis of esophageal cancer.