Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry

The reliable identification of diffuse large B-cell lymphoma (DLBCL)-specific targets owns huge implications for its diagnosis and treatment. Long non-coding RNAs (lncRNAs) are implicated in DLBCL pathogenesis; however, circulating DLBCL-related lncRNAs are barely investigated. The present study investigated plasma lncRNAs; HOX transcript antisense intergenic RNA (HOTAIR), Long intergenic RNA (Linc-p21), Growth arrest-specific 5 (GAS5) and X- inactive-specific transcript (XIST) as biomarkers for DLBCL diagnosis and responsiveness to Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Eighty-four DLBCL patients and thirty-three healthy controls were included. Only plasma HOTAIR, XIST and GAS5 were differentially expressed in DLBCL patients compared to controls. Pretreatment plasma HOTAIR was higher, whereas GAS5 was lower in non-responders than responders to R-CHOP. Plasma GAS5 was demonstrated superior diagnostic accuracy (AUC=0.97) whereas a panel of HOTAIR+GAS5 were superiorly discriminated responders from non-responders by receiver operating characteristics (ROC) analysis. In multivariate analysis, HOTAIR was an independent predictor of non-response. Among patients, plasma HOTAIR, Linc-p21 and XIST were correlated. Plasma GAS5 was negatively correlated with international prognostic index (IPI), whereas HOTAIR was positively correlated with performance status, denoting their prognostic potential

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