A novel disulfidptosis-related LncRNA prognostic risk model: predicts the prognosis, tumor microenvironment and drug sensitivity in esophageal squamous cell carcinoma.

Background: Disulfidptosis is a newly discovered type of cell death that differs from apoptosis, necrosis, ferroptosis and other death modes and is closely related to the occurrence and progression of tumors. However, the predictive potential and biological characteristics of disulfidptosis-related lncRNAs (DRGs-lncRNAs) in esophageal squamous cell carcinoma (ESCC) are unclear.

Methods: RNA transcriptome data, clinical information and mutation data for ESCC patients were obtained from The Cancer Genome Atlas (TCGA) database. Pearson correlation and Cox regression analyses were used to identify the DRGs-lncRNAs associated with overall survival (OS). LASSO regression analysis was used to construct the prognostic model. A nomogram was created to predict the prognosis of patients with ESCC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were used to identify the signaling pathways associated with the model. TIMER, CIBERSORT, ESTIMATE and other methods were used to analyze immune infiltration, immune function, immune checkpoints and drug sensitivity. The tumor mutation burden (TMB) were assessed between different risk groups. Real-time polymerase chain reaction (RT‒PCR) was used to detect the expression of DRGs-lncRNAs in ESCC cell lines.

Results: A total of 155 lncRNAs significantly associated with disulfidptosis were identified. Through univariate Cox regression analysis, LASSO regression analysis and multivariate Cox regression analysis, 9 lncRNAs with independent prognostic significance were selected, and a prognosis model was established. Survival analysis with the prognostic model revealed that there were obvious differences in survival between the high- and low-risk groups. Further analysis revealed that the immune microenvironment, immune infiltration, immune function, immune checkpoints, and drug sensitivity significantly differed between the high-risk and low-risk groups. Patients who exhibited both high risk and high tumor mutation burden (TMB) survived shorter, while those who fell into the low risk and low TMB categories survived longer. In addition, RT‒PCR analysis revealed differential expression of DRG lncRNAs between ESCC cell lines and esophageal epithelial cell lines.

Conclusions: We established a DRG-lncRNA prognostic model that can be used to predict the prognosis, tumor mutation burden, immune cell infiltration, and drug sensitivity of ECSS patients. The results of this study provide valuable insights into the understanding of ESCC and provide valuable assistance for the individualized treatment of ESCC patients.