Abstract
Objective Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive malignant tumor, accounting for 30-40% of non-Hodgkin's lymphoma. Our aim was to construct novel prognostic models of candidate genes based on clinical features. Methods RNA-seq and clinical data of DLBCL were retrieved from TCGA database. Coexpression modules were constructed by WGCNA. Then, we investigated the interactions between modules and clinical features. By overall survival analysis, prognostic candidate genes from modules of interest were identified. A coexpression network of prognostic candidate genes was then constructed through WGCNA. GEPIA was used to analyze the expression of a candidate gene between DLBCL and normal samples. Results 19 coexpression modules were constructed by 12813 genes from 52 DLBCL samples. The number of genes in modules ranged from 34 to 5457. We found that the purple module was significantly related with histological type (p value = 1e-04). Overall survival analysis revealed that MAFA-AS1, hsa-mir-338, and hsa-mir-891a were related with prognosis of DLBCL (p value = 0.027, 0.039, and 0.022, respectively). A coexpression network was constructed for the three prognostic genes. MAFA-AS1 was interacted with 36 genes, hsa-mir-891a was interacted with 11 genes, while no gene showed interaction with hsa-mir-338. Using GEPIA, we found that MAFA-AS1 showed low expression in DLBCL samples (p < 0.01). Conclusion We constructed a coexpression module related with histological type and identified three candidate genes (MAFA-AS1, hsa-mir-338, and hsa-mir-891a) that possessed potential value as prognostic biomarkers and therapeutic targets of DLBCL.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive malignant tumor originating from mature B-cells, accounting for 30-40% of nonHodgkin’s lymphoma [1, 2]
We found three candidate genes (MAFA-AS1, hsa-mir-891a, and hsamir-338) that were related with prognosis of DLBCL by overall survival analysis
Clinical and level3 RNA sequencing (RNA-seq) data of 51 DLBCL samples were retrieved from The Cancer Genome Atlas (TCGA)
Summary
DLBCL is a highly aggressive malignant tumor originating from mature B-cells, accounting for 30-40% of nonHodgkin’s lymphoma [1, 2]. Patients with DLBCL usually have a poor prognosis due to ineffective primary and second-line therapy or recurrence after stem cell transplantation [3]. Applicable prognostic parameters are necessary for clinicians, especially since new molecular markers have not yet entered clinical routines [4]. The International Prognostic Index (IPI) is the most common tool for risk stratification in DLBCL. Due to improved treatment options, pathobiology, and life expectancy of patients with DLBCL, IPI has been challenged [5]. It is necessary to propose novel prognostic models based on clinical features and prognostic biomarkers
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