Gene expression of activating transcription factor 5 as a predictor of survival in germinal cell diffuse large B-cell lymphoma

Martynchyk A., Kriachok I.A.

A. Martynchyk, I. Kriachok

National Cancer Institute, Kyiv, Ukraine

hematology@unci.org.ua

Introduction: Prognostic models based on currently used methods of prediction of the outcome in diffuse large B-cell lymphoma (DLBCL) do not identify the molecular basis of clinical heterogeneity. Aim: To identify new independent predictor of survival in germinal B-cell like subtype (GCB) of DLBCL. Patients and Methods: Analysis was performed on RAW data from 203 DLBCL samples from a previously stu­died cohort of patients treated with CHOP (Series 11318) using Partek Genomics Suite software (methods of regression analysis and Cox-model for prognostic significance of studied parameters). Study was conducted according to bioethical standards of National Cancer Institute (Kyiv, Ukraine). Only GCB samples were choosing for the next analysis. According to the IPI score 71 GCB samples were divided into two groups: with “high” IPI (3–4 risk factors, 14 samples) and “low” IPI (0–2 risk factors, 50 samples). Detection of differentially expressed genes was performed (IPI high vs low IPI). Gene list was created (fold changes < -1.3, > 1.3, p-value with FDR < 0.05). 37 differentially expressed genes were detected. Highest fold-change was in gene activating transcription factor 5 (ATF5). The medium expression of this gene in GCB subtype of DLBCL was 5.42 and the expression was higher in high IPI samples vs low IPI (7.5 vs. 4.9 respectively). GCB samples were divided into two groups depending on APF5 expression. In Kaplan — Meier survival analysis the probability of survival was better for patients with low expression of ATF5 compared to high expression. Results: Higher expression of ATF5 was observed in patients from high risk group (IPI score 3–4) (p-value with FDR 0.05) and the proba­bility of survival was less for this group of patients treated with CHOP, especially after one year of follow up. Conclusions: ATF5 could be a useful prognostic factor for DLBCL, but its significance need to be verified in further studies.

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