A Novel Defined Super-Enhancer Associated Gene Signature to Predict Prognosis in Patients With Diffuse Large B-Cell Lymphoma

Abstract

Background: Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease that can have profound differences in survival outcomes. A variety of powerful prognostic factors and models have been constructed; however, the development of more accurate prognosis prediction and targeted treatment for DLBCL still faces challenges. An explosion of research on super-enhancer (SE)–associated genes provide the possibility to use in prognostication for cancer patients. Here, we aimed to establish a novel effective prognostic model using SE-associated genes from DLBCL.Methods: A total of 1,105 DLBCL patients from the Gene Expression Omnibus database were included in this study and were divided into a training set and a validation set. A total of 11 SE-associated genes (BCL2, SPAG16, PXK, BTG1, LRRC37A2, EXT1, TGFBR2, ANKRD12, MYCBP2, PAX5, and MYC) were initially screened and identified by the least absolute shrinkage and selection operator (Lasso) penalized Cox regression, univariate and multivariate Cox regression analysis. Finally, a risk score model based on these 11 genes was constructed.Results: Kaplan–Meier (K–M) curves showed that the low-risk group appeared to have better clinical survival outcomes. The excellent performance of the model was determined via time-dependent receiver operating characteristic (ROC) curves. A nomogram based on the polygenic risk score was further established to promote reliable prognostic prediction. This study proposed that the SE-associated-gene risk signature can effectively predict the response to chemotherapy in DLBCL patients.Conclusion: A novel and reliable SE-associated-gene signature that can effectively classify DLBCL patients into high-risk and low-risk groups in terms of overall survival was developed, which may assist clinicians in the treatment of DLBCL.

Identification of somatic mutation-driven enhancers and their clinical utility in breast cancer

“…PXK was significantly associated with the prognosis of diffuse large B cell lymphoma. 17 The G > T mutation in the “chr9:65675405-65675906” significantly increased the activity of the enhancer (log2FC = 2.51) in LumB subtype, which in turn was associated with the downregulation of potential target genes, such as CBWD5 and ANKRD20A3P ( Figure 3 C; Table S1 ). The C > T mutation in “chr22:36194883-36195384” had the significantly upregulated the enhancer activity in LumA subtype, which in turn was associated with the upregulation of target genes TXN2, APOL1, APOL2, APOL3, APOL4, and EIF3D ( Figure 3 D; Table S1 ).…”

A novel signature constructed by super-enhancer-related genes for the prediction of prognosis in hepatocellular carcinoma and associated with immune infiltration

“…Oncogenic drivers known as super-enhancers, which are characterized by massive clusters of enhancers, have been shown to be crucial for maintaining cancer cell identity. It has been reported that SE significantly impacts the development of malignancies, and SE-related genes can serve as prognostic markers ( 7 , 8 , 12 , 13 ). However, no studies have demonstrated the correlations between the SE-related genes and prognosis in HCC.…”

Superenhancers as master gene regulators and novel therapeutic targets in brain tumors

“…In addition, SEs with broad and high H3K27ac signals have been identified in nasopharyngeal carcinoma and were found to be associated with overexpression of the ETV6 oncogene and poor prognosis 121 . Xu et al defined an SEassociated gene risk signature to predict the response to chemotherapy in patients with diffuse large B-cell lymphoma, which may help clinicians make more appropriate treatment decisions 122 . Moreover, in our previous studies, we constructed prognostic models based on SE-associated genes to predict overall survival for osteosarcoma and multiple myeloma patients, which may be helpful for clinical treatment 123,124 .…”