A multi-programmed cell death-related LncRNA signature for prognosis and immune microenvironment evaluation in kidney...

Kidney renal clear cell carcinoma (KIRC) shows substantial prognostic heterogeneity, motivating robust transcriptome-based risk stratification. Ferroptosis, cuproptosis and disulfidptosis are distinct stress-related cell-death programs whose gene-expression patterns may capture diverse tumour states. Using TCGA-KIRC RNA-seq data (n=533), tumour samples were randomly split 1:1 into a training set (n=267) and an independent test set (n=266); In the training cohort, lncRNAs associated with curated genes for each programmed cell death (PCD) modality were screened using EPIC-adjusted partial Spearman correlations (-r->0.4, FDR<0.05) and differential expression versus adjacent normal tissues (p<0.05). The intersection across modalities yielded 176 multi-PCD-related lncRNAs. Univariate Cox analysis, LASSO-Cox regression and multivariate Cox modelling identified a six-lncRNA signature (AC026401.3, GAS5-AS1, SNHG8, AC084024.4, LINC02027 and AC115522.1) to compute a risk score. High-risk patients had significantly poorer overall and progression-free survival in both training and test cohorts, with stable time-dependent discrimination (AUCs 0.765/0.752/0.751 at 1/3/5 years in the full cohort). Computational analyses suggested risk-associated differences in immune contexture and predicted immune escape, and mutation profiling indicated higher VHL and PBRM1 alteration frequencies in the high-risk group. This signature supports prognostic stratification in KIRC and provides an association-based framework for further validation.