Identification and Validation of Ferroptosis-Related LncRNAs Signature as a Novel Prognostic Model for Chronic Lymphocytic Leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a subtype of B-cell malignancy with high heterogeneity. Ferroptosis is a novel cell death induced by iron and lipid peroxidation and exhibits prognostic value in many cancers. Emerging studies on long non-coding RNAs (lncRNAs) and ferroptosis reveal the unique value in tumorigenesis. However, the prognostic value of ferroptosis-related lncRNAs (FRLs) remains unclear in CLL.

AIM: We aimed to construct a FRLs risk model to predict prognosis and improve prognostic stratification for clinical practice.

METHODS: RNA-sequencing data and clinical characteristics of CLL patients were downloaded from the GEO database. Based on ferroptosis-related genes from FerrDb database, differentially expressed FRLs with prognostic significance were identified and used to generate the risk model. The capability of the risk model was assessed and evaluated. GO and KEGG analyses were performed to confirm biological roles and potential pathways.

RESULTS: A novel ferroptosis-related lncRNAs prognostic score (FPS) model containing six FRLs (PRKCQ, TRG.AS1, LNC00467, LNC01096, PCAT6 and SBF2.AS1) was identified. Patients in the training and validation cohort were evenly divided into high- and low-risk groups. Our results indicated that patients in the high-risk group had worse survival than those in the low-risk group. Functional enrichment analyses showed that the differently expressed genes (DEGs) between the two groups were enriched in the chemokine signaling pathway, hematopoietic cell lineage, T cell differentiation, TCR pathway and NF-κB pathway. Moreover, significant differences in immune cell infiltration were also observed. Surprisingly, FPS was proved to be an independent prognostic indicator for OS.

CONCLUSION: We established and evaluated a novel prognostic risk model with 6 FRLs that could predict prognosis accurately and describe the distinct immune infiltration in CLL.