KEY TAKEAWAYS
- The study aimed to investigate the impact of the cuproptosis-associated gene DKC1 on the malignant progression and prognosis of esophageal cancer.
- Researchers noted that DKC1’s role in tumor progression highlights its potential as a diagnostic and therapeutic target.
Esophageal cancer is a prevalent malignancy of the digestive tract, with a poor overall prognosis despite advances in treatment. Cuproptosis, a type of programmed cell death, impacts tumor progression.
Daidi Zhang and the team aimed to evaluate the influence of the cuproptosis-associated gene DKC1 on esophageal cancer progression.
They performed an inclusive analysis using clinical and RNA sequencing data from patients with esophageal cancer sourced from The Cancer Genome Atlas (TCGA). Univariate Cox regression analysis was employed to identify cuproptosis-related differentially expressed genes linked to prognosis. The expression differences of DKC1 between tumor and normal tissues were validated through three-dimensional multiomics difference analysis.
The association between DKC1 expression and the tumor microenvironment (TME) was examined using the TIMER2.0 algorithm and further corroborated with 96 single-cell datasets from the TISCH database. Additionally, the functional role of DKC1 in pancarcinoma was explored through Gene Set Enrichment Analysis (GSEA).
A comprehensive pan-cancer survival map was constructed, and DKC1 expression across various molecular subtypes was verified. Drug sensitivity connections with DKC1 were established using the CellMiner, GDSC, and CTRP databases. Finally, the involvement of DKC1 in esophageal cancer progression was investigated through both in vivo and in vitro experiments.
About the copper death-related gene DKC1 identified in esophageal cancer, varying levels of DKC1 expression were observed across different tumor types. Analysis revealed a correlation between DKC1 expression and clinical features, associating it with common cell cycle pathways and multiple metabolic pathways. High DKC1 expression was found to predict poor prognosis in patients with various tumors and affect drug sensitivity.
Significant associations were also noted between DKC1 expression and molecules involved in immune regulation and lymphocyte subtype infiltration. The increased expression of DKC1 in esophageal cancer tissues was confirmed using clinical tissue samples. Additionally, DKC1-mediated promotion of esophageal cancer cell proliferation and migration was validated through both in vitro and in vivo experiments. Furthermore, it is suggested that DKC1 may play a role in the regulation of cuproptosis.
The study concluded that DKC1, through its systematic analysis and experimental validation, demonstrates strong diagnostic and prognostic potential across various cancers. Further research suggests that DKC1 may play a significant role in reshaping the TME, underscoring its potential as a target for cancer treatment and its usefulness in predicting responses to chemotherapy.
This study was funded by the National Natural Science Foundation of China and the Key Project of Science and Technology of Henan Province.
Source: https://pubmed.ncbi.nlm.nih.gov/39103487/
Zhang D, Zhu Q, Huang X, et al. (2024). “Identifying and validating the roles of the cuproptosis-related gene DKC1 in cancer with a focus on esophageal carcinoma.” J Cancer Res Clin Oncol. 2024;150(8):382. Published 2024 Aug 5. doi:10.1007/s00432-024-05870-8
