Comprehensive Analysis of Eph-Ephrin as Novel DLBC Biomarkers for Molecular Subtyping and the Predictability in Prognosis and Drug Response

Abstract Background: Receptor tyrosine kinases (RTKs) are key signal molecules for sustaining proliferative signaling and abnormal of RTKs appears in many cancers, including Lymphoid Neoplasm Diffuse Large B-cell Lymphoma (DLBC).Methods: Cluster analysis based on RNA-seq and RPPA data were calculated to establish novel signature for molecular subtyping of DLBC. Principal component analysis (PCA) was used to evaluation relationship of selected genes.Results: EPHB4, EPHB6, EFNA3, EFNA4, EFNB1 are 5 specific genes in DLBC and their expression level are significantly relevant to poor prognosis. Integration analysis of DLBC Expr-Ab signature discovered five DLBC related Eph-Ephrin genes may be involved in epigenetic regulation in DLBC progress. Four novel clusters based on Expr-Ab are generated and we first link five Eph-Ephrin to well-defined oncogenes as following: EPHB4-BCL6; EFNA3/EFNA4-MYC; EPHB6-EZH2; EFNB1-Epigenetic modulators. Drug response data involving 13 traditional and targeting drugsConclusions: Expr-Ab signature we established in this study indicates the power of both RNA-seq and RPPA data in developing and evaluating precision regimens. We also highlight Eph-Ephrin, as surface proteins, are powerful potentially biomarkers. Our finding underlines Eph-Ephrin as biomarkers for predicting prognosis and precision regimen for patients with lymphoma.