Investigating the prognostic value of non-coding RNAs in chronic lymphocytic leukemia: insights from a systematic review and meta-analysis.

BACKGROUND: Non-coding RNA (ncRNA) expression dysregulation has been implicated in the prognosis of various cancers. Several mechanisms have been associated with altered expression of the ncRNAs with the progression of chronic lymphocytic leukemia (CLL). Based on the special properties that ncRNAs possess, including their stability, tissue specificity, and disease-associated dysregulation, a considerable amount of research has been conducted to identify their potential as non-invasive prognostic biomarkers. METHODS: A comprehensive search was conducted in WOS, Scopus, PubMed, Embase, and ProQuest, in accordance with PRISMA guidelines. Hazard ratios (HRs) were used to assess the prognostic value of ncRNA dysregulation in CLL. Risk of bias was evaluated with the QUIPS tool, and subgroup analyses were based on sample size and study quality. Publication bias was assessed using Egger’s, Begg’s, and Trim-and-Fill tests. Sensitivity analysis employed the leave-one-out method, and evidence certainty was graded using the modified GRADE framework. RESULTS: Our analysis included 4905 CLL patients. Dysregulated miRNAs were associated with shorter overall survival (OS) (HR: 2.41), progression-free survival (PFS) (HR: 1.82), and time to treatment (TTT) (HR: 2.39) in CLL patients. Dysregulation of lncRNAs was linked to poorer OS (HR: 2.76) and earlier TTT initiation (HR: 2.53). Additionally, dysregulation of circRNAs was associated with poorer OS (HR: 3.91). CONCLUSION: Our comprehensive meta-analysis results showed that dysregulation of ncRNAs, including miRNAs, lncRNAs, and circRNAs, was associated with poor clinical outcomes in parameters such as OS, PFS, and TTT, identifying them as moderate prognostic markers for CLL patients.