Identification of an individualized RNA binding protein‐based prognostic signature for diffuse large B‐cell lymphoma

Abstract

RNA binding proteins (RBPs) are increasingly appreciated as being essential for normal hematopoiesis and have a critical role in the progression of hematological malignancies. However, their functional consequences and clinical significance in diffuse large B‐cell lymphoma (DLBCL) remain unknown. Here, we conducted a systematic analysis to identify RBP‐related genes affecting DLBCL prognosis based on the Gene Expression Omnibus database. By univariate and multivariate Cox proportional hazards regression (CPHR) methods, six RBPs‐related genes (CMSS1, MAEL, THOC5, PSIP1, SNIP1, and ZCCHC7) were identified closely related to the overall survival (OS) of DLBCL patients. The RBPs signature could efficiently distinguished low‐risk from high‐risk patients and could serve as an independent and reliable factor for predicting OS. Moreover, Gene Set Enrichment Analysis revealed 17 significantly enriched pathways between high‐ versus low‐risk group, including the regulation of autophagy, chronic myeloid leukemia, NOTCH signaling pathway, and B cell receptor signaling pathway. Then we developed an RBP‐based nomogram combining other clinical risk factors. The receiver operating characteristic curve analysis demonstrated high prognostic predictive efficiency of this model with the area under the curve values were 0.820 and 0.780, respectively, in the primary set and entire set. In summary, our RBP‐based model could be a novel prognostic predictor and had the potential for developing treatment targets for DLBCL.

An Autophagy-Related Gene Signature can Better Predict Prognosis and Resistance in Diffuse Large B-Cell Lymphoma

“…There was a good consistency with the findings of recent studies. Xie and his colleagues constructed an RNA binding protein-based prognostic signature for diffuse large B-cell lymphoma and also found that the activation of autophagy was associated with high-risk patients who had poor outcomes ( Xie et al, 2021 ).…”

Identification of three small nucleolar RNAs (snoRNAs) as potential prognostic markers in diffuse large B‐cell lymphoma

“…For instance, using the GSE11318 dataset, Xie et al established a prognostic risk model using six related genes of RNA‐binding proteins, and achieved an the AUC value was 0.65 at 3 years. 49 Zhang et al constructed a risk model with an AUC of 0.564 based on alternative splicing events in DLBCL. 50 Zhou et al reported that the AUC of the immunoscore prognostic signature in DLBCL was 0.562.…”

“…The AUC for this snoRNA model was 0.663 at 3 years, showing a certain predictive capacity after comparison with the published prognostic models, suggesting the possibility of clinical application in DLBCL patients. For instance, using the GSE11318 dataset, Xie et al established a prognostic risk model using six related genes of RNA‐binding proteins, and achieved an the AUC value was 0.65 at 3 years 49 . Zhang et al constructed a risk model with an AUC of 0.564 based on alternative splicing events in DLBCL 50 .…”

Emerging roles for heterogeneous ribonuclear proteins in normal and malignant B cells

“…Perturbations in the RBP-RNA network have been causally associated with many B cell malignancies. For example, it was recently reported that RBPs play important roles in diffuse large B cell lymphoma (DLBCL) biology and are significantly associated with overall survival (Xie et al 2021). In Burkitt lymphoma (BL), HNRNPU is recurrently mutated with many mutations predicted to truncate the protein (Thomas et al 2022); however, the mechanisms by which hnRNP U and other hnRNPs contribute to pathology largely remain hypothetical.…”