Systematic Analysis of Competing Endogenous RNA Networks in Diffuse Large B-Cell Lymphoma and Hodgkin's Lymphoma.

Abstract

Lymphoma is a systemic malignancy, originating from the lymphatic system, which accounts for 3 to 4% of all tumors. There are two major subtypes of lymphoma, namely, diffuse large B-cell lymphoma (DLBCL) and Hodgkin’s lymphoma (HL). Elucidation of the pathogenesis of these two lymphoma types is crucial for the identification of potential therapeutic targets. Compared with the corresponding knowledge of other diseases, the understanding of the regulatory networks involved in DLBCL and HL is relatively deficient. To address this, we comprehensively analyzed the mRNAs, lncRNAs, and miRNAs that were differentially expressed between normal and tumor samples of DLBCL and HL. In addition, functional enrichment analysis of the differentially expressed mRNAs was performed. We constructed two specific ceRNA networks of DLBCL and HL. The pathways enriched by dysregulated mRNAs in DLBCL and HL were mainly involved in immune responses, transcription process, and metabolism process. The ceRNA network analysis revealed that 45 ceRNAs were shared between the two ceRNA networks, including five pivotal lncRNAs (MALAT1, CTBP1-AS, THUMPD3-AS, PSMA3-AS1, and NUTM2A-AS1). In addition, we proposed a DLBCL survival risk model based on a DLBCL-specific network constructed by Lasso regression analysis. The model, which is based on eight mRNAs, exhibited excellent performance in regard to predicting outcomes in DLBCL patients, with a p value of 0.0017 and AUC of 0.9783. In summary, although the molecular mechanisms underlying tumorigenesis in DLBCL and HL were quite different, the same pivotal lncRNAs acted as key regulators. Our findings identify novel potential prognostic and therapeutic targets for DLBCL and HL.