Research Paper Volume 15, Issue 24 pp 15535—15556
Potential impact of cuproptosis-related genes on tumor immunity in esophageal carcinoma
- 1 Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China
- 2 Graduate school of Hebei Medical University, Shijiazhuang, China
- 3 Department of Thoracic Surgery, Hebei Chest Hospital, Shijiazhuang, China
- 4 Department of Thoracic Surgery, Affiliated Hospital of Chengde Medical University, Chengde, China
- 5 Clinical Laboratory Center, The Second Hospital of Hebei Medical University, Shijiazhuang, China
Received: July 10, 2023 Accepted: November 7, 2023 Published: December 30, 2023
https://doi.org/10.18632/aging.205391How to Cite
Copyright: © 2023 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Cuproptosis involves a direct interaction with the tricarboxylic acid (TCA) lipid acylation components. This process intricately intersects with post-transcriptional lipid acylation (LA) and is linked to mitochondrial respiration and LA metabolism. Copper ions form direct bonds with acylated DLAT, promoting DLAT oligomerization, reducing Fe-S cluster proteins, and inducing a protein-triggered toxic stress response that culminates in cell demise. Simultaneously, the importance of immune contexture in cancer progression and treatment has significantly increased. We assessed the expression of cuproptosis-related genes (CRGs) across TCGA and validated our findings using the GEO data. Consensus clustering divided esophageal cancer (ESCA) patients into two clusters based on the expression of 7 CRGs. We evaluated the expression of immune checkpoint inhibitor (ICI) targets and calculated the elevated tumor mutational burden (TMB). Weighted gene co-expression network analysis (WGCNA) identified genes associated with the expression of CRGs and immunity. Cluster 1 exhibited increased immune infiltration, higher expression of ICI targets, higher TMB, and a higher incidence of deficiency in mismatch repair-microsatellite instability-high status. WGCNA analysis identified 14 genes associated with the expression of CRGs and immune scores. ROC analysis revealed specific hub genes with strong predictive capabilities. The expression levels of SLC6A3, MITD1, and PDHA1 varied across different pathological stages; CCS, LIPT2, PDHB, and PDHA1 showed variation in response to radiation therapy; MITD1 and PDHA1 exhibited differences related to the pathological M stages of ESCA. CRGs influence the immune contexture and can potentially transform cold tumors into hot tumors in ESCA patients.
Abbreviations
LA: lipid acylation; ESCA: esophageal carcinoma; EAC: esophageal adenocarcinoma; TCA: tricarboxylic acid; VEGF: vascular endothelial growth factor; BRAF: v-raf murine sarcoma viral oncogene homolog B1; TM: tetrathiomolybdenate; CRGs: cuproptosis-related genes; TCGA: The Cancer Genome Atlas; PPI: protein-protein interactions; MDSCs: myeloid-derived suppressor cells; GSEA: gene set enrichment analysis; SNPs: single nucleotide polymorphisms; SNV: single nucleotide variant; TMB: tumor mutational burden; WGCNA: weighted gene co-expression network analysis; GEO: Gene Expression Omnibus; AUC: area under curve; ROS: reactive oxygen species; DCs: dendritic cells; ICIs: immune checkpoint inhibitors; PD-1: targeting programmed cell death 1; TME: tumor microenvironment; GSVA: gene set variation analysis; DEGs: differentially expressed genes; GO: gene ontology.