Identification of gene modules associated with survival of diffuse large B-cell lymphoma treated with CHOP-based chemotherapy

Abstract

Diffuse Large B-cell Lymphoma (DLBCL), a heterogeneous disease, is influenced by complex network of gene interactions. Most previous studies focused on individual genes, but ignored the importance of intergenic correlations. In current study, we aimed to explore the association between gene networks and overall survival (OS) of DLBCL patients treated with CHOP-based chemotherapy (cyclophosphamide combination with doxorubicin, vincristine and prednisone). Weighted gene co-expression network analysis was conducted to obtain insights into the molecular characteristics of DLBCL. Ten coexpression gene networks (modules) were identified in training dataset (n = 470), and their associations with patients' OS after chemotherapy were tested. The results were validated in four independent datasets (n = 802). Gene ontology (GO) biological function enrichment analysis was conducted with Metascape. Three modules (purple, brown and red), which were enriched in T-cell immune, cell-cell adhesion and extracellular matrix (ECM), respectively, were found to be related to longer OS. Higher expression of several hub genes within these three co-expression modules, for example, LCP2 (HR = 0.77, p = 5.40 × 10 −2 ), CD2 (HR = 0.87, p = 6.31 × 10 −2 ), CD3D (HR = 0.83, p = 6.94 × 10 −3 ), FYB (HR = 0.82, p = 1.40 × 10 −2 ), GZMK (HR = 0.92, p = 1.19 × 10 −1 ), FN1 (HR = 0.88, p = 7.06 × 10 −2 ), SPARC (HR = 0.82, p = 2.06 × 10 −2 ), were found to be associated with favourable survival. Moreover, the associations of the modules and hub genes with OS in different molecular subtypes and different chemotherapy groups were also revealed. In general, our research revealed the key gene modules and several hub genes were upregulated correlated with good survival of DLBCL patients, which might provide potential therapeutic targets for future clinical research.

High Expression of VAV Gene Family Predicts Poor Prognosis of Acute Myeloid Leukemia

“…36 A systematic study of diffuse large B-cell lymphoma has shown that LCP2 is a prognostic marker and its high expression is associated with good survival. [37][38][39] These results confirmed that the functional module identified in our study has important significance in hematological tumors.…”

CHN1 is a Novel Prognostic Marker for Diffuse Large B-Cell Lymphoma

“…CD3D, CLU, ICOS, KLRB1 and LAT appear to be prognostic factors in a range of malignancies, such as B-NHL, 19 , 20 colorectal cancer, 21 , 22 ovarian cancer, 23 bladder cancer, 24 breast cancer, 25 , 26 cervical cancer, 27 and lung cancer, 28–31 and play important roles in lymphoma development. 32–36 Of note, the role and prognostic value of CHN1 in B-NHL have never been reported before, so we focused our attention on CHN1 in this study.…”

“…Kaplan-Meier curves showed that the high expression of these genes was correlated with a prolonged survival time in both GSE10846 (Figure 3A-F, p < 0.05) and GSE117556 (Figure 3G-L, p < 0.05). CD3D, CLU, ICOS, KLRB1 and LAT appear to be prognostic factors in a range of malignancies, such as B-NHL, 19,20 colorectal cancer, 21,22 ovarian cancer, 23 bladder cancer, 24 breast cancer, 25,26 cervical cancer, 27 and lung cancer, [28][29][30][31] and play important roles in lymphoma development. [32][33][34][35][36] Of note, the role and prognostic value of CHN1 in B-NHL have never been reported before, so we focused our attention on CHN1 in this study.…”

Computational prediction of CRISPR-impaired non-coding regulatory regions

“…Another candidate is the NT5C2 gene, which is known to confer treatment resistance against thiorubin in acute lymphocytic leukemias [41]. For ANXA7 it was shown that resistance in different cancer types has been observed [43,44].…”