Prognostic implications of a programmed cell death-related long non-coding RNA signature and its relevance to immune features in esophageal carcinoma

Esophageal carcinoma (ESCA) is a highly lethal malignancy with poor prognosis and limited treatment options. The identification of effective prognostic biomarkers and therapeutic targets remains an important goal in improving outcomes for patients with ESCA. While the involvement of programmed cell death (PCD) mechanisms in cancer remains underexplored, they are thought to influence some aspects of tumor biology. The purpose of this study was to construct a prognostic signature derived from PCD-related long non-coding RNAs (lncRNAs) in ESCA.

Transcriptome and clinical data from ESCA patients were sourced from The Cancer Genome Atlas (TCGA) database. Candidate lncRNAs associated with PCD and patient prognosis were identified and subjected to univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression to build a prognostic signature. The signature's predictive performance was validated internally. To explore possible mechanisms underlying risk stratification, we employed multiple approaches, including weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis (GSEA), and assessment of immune cell infiltration patterns.

Eight PCD-related lncRNAs (AC109347.1, BLACE, AP001527.2, AP001001.1, LINC00402, AC087289.5, FAM83C-AS1, and AL132655.2) were screened and incorporated into the prognostic signature. The signature appeared capable of distinguishing between high- and low-risk groups with distinct survival outcomes. Downregulation of immune-related pathways was observed in high-risk patients based on WGCNA and GSEA analyses. Immune cell infiltration and immune scoring metrics were comparatively lower in high-risk individuals. Based on drug response predictions, we identified potential agents that could be preferentially effective in high-risk ESCA patients.

In conclusion, the PCD-related lncRNAs signature constructed in this study may contribute to prognosis assessment in ESCA and offers preliminary indications of immune involvement worthy of further investigation.