Bioinformatics and clinical analysis reveal the potential diagnostic and prognostic role of DLD for pan cancer and renal carcinoma

Cuprotosis is recognized as a novel form of programmed cell death pathway. Dihydrolipoamide dehydrogenase (DLD) functions as a critical gene regulating cuprotosis. Here, we designed to analyze the utility of consideration of the prognostic and immunological significance of cuproptosis-related gene DLD across human cancers. Utilizing the TCGA, GTEx, and HPA databases, this study systematically evaluated DLD expression at both the mRNA and protein levels. Our analysis leveraged TCGA data to explore how DLD relates to survival, clinical features, immune infiltration, and DNA methylation in pan-cancer. Single-cell sequencing data from TISCH complemented this by resolving DLD expression at the cellular level. Experimental validation in KIRC was conducted via IHC, western blot, and qRT-PCR. Together, these approaches aimed to define the oncogenic role of DLD, particularly in KIRC. The Wilcoxon rank sum test, Pearson correlation test are used to teste differences among groups and correlations. The Kaplan–Meier method is used to estimate the relationship between patient prognosis and DLD expression levels. DLD exhibits elevated expression across multiple malignancies, and its high expression consistently correlates with improved clinical prognosis (p < 0.05). Bioinformatic analyses further show significant correlations between DLD expression and the activity of cancer-related pathways, as well as immunological interactions including cancer-associated fibroblasts, immune cell infiltration, and immune checkpoint genes. Single-cell analysis suggests DLD likely participates in angiogenesis, cell cycle regulation, differentiation, DNA damage, DNA repair, and hypoxia responses. Notably, experimental validation confirms significantly lower DLD expression in KIRC tissues. Moreover, DLD expression correlates significantly with TNM stage, pathological stage, histologic grade, and primary therapy outcome (all p < 0.05). The cuproptosis-related gene DLD may be a potential diagnostic and prognostic biomarker for pan-cancer. Furthermore, it may serve as an independent risk factor for poor outcomes of KIRC patients.