Department of Medicine, Shanghai Di An Medical Laboratory Co., Ltd, Shanghai, 200433, China.
Department of Orthopedic Oncology, Changzheng Hospital, Naval Medical University, Shanghai, 200003, China.
Curr Med Sci. 2022 Aug;42(4):754-768. doi: 10.1007/s11596-022-2612-6. Epub 2022 Aug 9.
Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma. Due to its genetic heterogeneity and abnormal metabolism, many DLBCL patients have a poor prognosis. This study investigated the key metabolism-related genes and potential mechanisms.
Differentially expressed genes, differentially expressed transcription factors (TFs), and differentially expressed metabolism-related genes (DEMRGs) of glucose and lipid metabolic processes were identified using the edgeR package. Key DEMRGs were screened by Lasso regression, and a prediction model was constructed. The cell type identification by estimating relative subsets of RNA transcripts algorithm was utilized to assess the fraction of immune cells, and Gene Set Enrichment Analysis was used to determine immune-related pathways. A regulatory network was constructed with significant co-expression interactions among TFs, DEMRGs, immune cells/pathways, and hallmark pathways.
A total of 1551 DEMRGs were identified. A prognostic model with a high applicability (area under the curve=0.921) was constructed with 13 DEMRGs. Tumorigenesis of DLBCL was highly related to the neutrophil count. Four DEMRGs (PRXL2AB, CCN1, DECR2 and PHOSPHO1) with 32 TF-DEMRG, 36 DEMRG-pathway, 14 DEMRG-immune-cell, 9 DEMRG-immune-gene-set, and 67 DEMRG-protein-chip interactions were used to construct the regulatory network.
We provided a prognostic prediction model based on 13 DEMRGs for DLBCL. We found that phosphatase, orphan 1 (PHOSPHO1) is positively regulated by regulatory factor X5 (RFX5) and mediates MYC proto-oncogene (MYC) targeting the V2 pathway and neutrophils.
弥漫性大 B 细胞淋巴瘤（DLBCL）是一种侵袭性非霍奇金淋巴瘤。由于其遗传异质性和代谢异常，许多 DLBCL 患者预后不良。本研究探讨了关键代谢相关基因和潜在机制。
使用 edgeR 包鉴定葡萄糖和脂质代谢过程中的差异表达基因、差异表达转录因子（TF）和差异表达代谢相关基因（DEMRG）。通过 Lasso 回归筛选关键 DEMRG，并构建预测模型。使用估计相对 RNA 转录物子集算法的细胞类型识别来评估免疫细胞的分数，并进行基因集富集分析以确定免疫相关途径。通过 TF、DEMRG、免疫细胞/途径和标志性途径之间的显著共表达相互作用构建调控网络。
共鉴定出 1551 个 DEMRG。构建了一个具有高适用性的预后模型（曲线下面积=0.921），该模型由 13 个 DEMRG 组成。DLBCL 的肿瘤发生与中性粒细胞计数高度相关。四个 DEMRG（PRXL2AB、CCN1、DECR2 和 PHOSPHO1）与 32 个 TF-DEMRG、36 个 DEMRG-途径、14 个 DEMRG-免疫细胞、9 个 DEMRG-免疫基因集和 67 个 DEMRG-蛋白质芯片相互作用用于构建调控网络。
我们提供了一个基于 13 个 DEMRG 的 DLBCL 预后预测模型。我们发现磷酸酶孤儿 1（PHOSPHO1）受调节因子 X5（RFX5）的正向调控，并介导 MYC 原癌基因（MYC）靶向 V2 途径和中性粒细胞。
