Multi‑cohort Validation Based on Disulfidptosis-Related lncRNAs for Predicting Prognosis and Immunotherapy Response of Esophageal Squamous Cell Carcinoma.

Abstract

Background: Disulfidptosis, a novel pattern of regulatory cell death, provides a valuable opportunity to gain deeper comprehension of tumor pathogenesis and treatment strategies. However, its biological mechanism in esophageal squamous cell carcinoma (ESCC) has yet to be completely elucidated.

Materials and methods: From the Gene Expression Omnibus (GEO) GSE53625 dataset, we obtained RNA-seq data and clinical information. An analysis of Pearson correlation was utilized to screen disulfidptosis-related lncRNAs (DRLs), followed by LASSO and multivariate Cox regression analysis to construct a prognostic signature. The reliability and accuracy of this signature were verified on internal validation sets, including training (n= 90), testing (n= 89), and GSE53625 entire (n= 179) sets, as well as external sets, including TCGA-ESCC (n= 81) and GSE53624 (n= 119) sets. Additionally, mutation data comes from TCGA database was utilized for validating tumor mutation burden (TMB) analysis. In cell lines, an analysis of lncRNA differential expression was conducted using qRT-PCR.

Results: Ultimately, six DRLs were utilized to construct a prognostic signature. Across all sets, Kaplan-Meier analysis indicated that high-risk ESCC patients have a poorer prognosis (p < 0.05), and ROC analysis showed that the AUC values at 1, 3, and 5 years all exceeded 0.6. Moreover, disparities were observed in immune phenotype scores, tumor infiltration of immune cells, functional enrichment, TIDE score, immune function, and TMB among the two risk groups. Additionally, individuals at high risk showed higher sensitivity to erlotinib, acetalax, gefitinib, lapatinib, sapitinib, and afatinib.

Conclusion: Through bioinformatics analysis, a novel and robust DRLs signature for ESCC was established, providing new insights into the prognosis prediction and potential treatment strategies. Nevertheless, this study is retrospective and relies on public databases, with a limited sample size within the datasets. In the future, it is essential to conduct more extensive validation of the prognostic value and efficacy in real ESCC cohorts.