Abstract
BACKGROUND: Accumulating evidence indicates that the aberrantly expressed long non-coding RNA DLEU1 may serve as a potential therapeutic target and prognostic biomarker in various cancers; however, these findings remain inconclusive. This study systematically evaluated the prognostic value of DLEU1 via a meta-analysis, while also summarizing its biological functions and underlying mechanisms in malignancies. METHODS: A systematic literature search was performed in PubMed, Web of Science, Embase, and the Cochrane Library from inception until October 10, 2025. Pooled hazard ratios or odds ratios with 95% confidence intervals were calculated to assess the associations between DLEU1 expression and patient survival or clinicopathological parameters. These findings were subsequently validated using the GEPIA2 platform. Potential target genes of DLEU1 were predicted via the StarBase database, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Additionally, we systematically reviewed and summarized the reported functional roles and molecular mechanisms of DLEU1 over the past five years. RESULTS: This meta-analysis, incorporating nine studies with a total of 938 cancer patients, demonstrated that elevated DLEU1 expression was significantly associated with shortened overall survival and adverse clinicopathological features, including lymph node metastasis and advanced TNM stage. In contrast, no significant correlations were observed with age, gender, tumor size, or tumor differentiation. Independent validation via the GEPIA2 database confirmed DLEU1 upregulation in six cancer types and its correlation with poorer survival. Furthermore, a total of 254 potential target genes of DLEU1 were identified through StarBase, and these target genes were significantly enriched in various cancer-related pathways, such as Rap1 signaling pathway, cAMP signaling pathway, PI3K-Akt signaling pathway, apoptosis, and calcium signaling pathway. CONCLUSION: Upregulated expression of lncRNA DLEU1 is associated with adverse clinicopathological features and poor prognosis in cancer patients, establishing it as a promising prognostic biomarker and therapeutic target across multiple malignancies. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251167807.