Circulating lncRNA-and miRNA-Associated ceRNA Network as a Potential Prognostic Biomarker for Non-Hodgkin Lymphoma: A Bioinformatics Analysis and a Pilot Study

Abstract

Non-Hodgkin lymphoma (NHL) is characterized by a great variability in patient out-comes, resulting in the critical need for identifying new molecular prognostic biomarkers. This study aimed to identify novel circulating prognostic biomarkers based on an miRNA/lncRNA-as-sociated ceRNA network for NHL. Using bioinformatic analysis, we identified the miRNA-lncRNA pairs, and using RT-qPCR, we analyzed their plasma levels in a cohort of 113 NHL patients to assess their prognostic value. Bioinformatic analysis identified SNHG16 and SNHG6 as hsa-miR-20a-5p and hsa-miR-181a-5p sponges, respectively. Plasma levels of hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNG6 were significantly associated with more aggressive disease and IPI/FLIPI scores. Moreover, we found that patients with risk expression profiles of hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNHG6 presented a higher risk of positive bone marrow involvement. Moreover, hsa-miR-20a-5p/SNHG16 and hsa-miR-181a-5p/SNHG6 pairs’ plasma levels were associated with overall survival and progression-free survival of NHL patients, being independent prognostic factors in a multivariate Cox analysis. The prediction models incorporating the ceRNA network expression analysis improved the predictive capacity compared to the model, which only considered the clini-copathological variables. There are still few studies on using the ceRNA network as a potential prognostic biomarker, particularly in NHL, which may permit the implementation of a more personalized management of these patients.