Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China.
State Key Laboratory of Experimental Hematology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Cell Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.
Front Immunol. 2022 Jul 6;13:813031. doi: 10.3389/fimmu.2022.813031. eCollection 2022.
Diffuse large B-cell lymphoma (DLBCL) is a biologically and clinically heterogeneous disease that requires personalized clinical treatment. To assign patients into different risk categories, cytogenetic abnormalities and genetic mutations have been widely applied to the prognostic stratification of DLBCL. Increasing evidence has demonstrated that deregulated epigenetic modifications and long noncoding RNAs (lncRNAs) contribute to the initiation and progression of DLBCL. However, specific lncRNAs that affect epigenetic regulation and their value in predicting prognosis and therapy response remain uncertain. Here, 2,025 epigenetic-related genes were selected, and 9 lncRNAs (PRKCQ-AS1, C22orf34, HCP5, AC007389.3, APTR, SNHG19, ELFN1-AS1, LINC00487, and LINC00877) were tested and validated to establish an lncRNA-regulating epigenetic event signature (ELncSig). ELncSig, which was established based on independent lymphoma datasets, could distinguish different survival outcomes. Functional characterization of ELncSig showed that it could be an indicator of the immune microenvironment and is correlated with distinctive mutational characteristics. Univariate and multivariate analyses showed that ELncSig was independent of traditional prognostic factors. The novel immune-related ELncSig exhibits promising clinical prognostic value for DLBCL.
弥漫性大 B 细胞淋巴瘤(DLBCL)是一种生物学和临床异质性疾病,需要个性化的临床治疗。为了将患者分配到不同的风险类别中,细胞遗传学异常和基因突变已广泛应用于 DLBCL 的预后分层。越来越多的证据表明,失调的表观遗传修饰和长非编码 RNA(lncRNA)有助于 DLBCL 的发生和进展。然而,影响表观遗传调控的特定 lncRNA 及其在预测预后和治疗反应方面的价值仍不确定。在这里,选择了 2025 个与表观遗传相关的基因,并测试和验证了 9 个 lncRNA(PRKCQ-AS1、C22orf34、HCP5、AC007389.3、APTR、SNHG19、ELFN1-AS1、LINC00487 和 LINC00877),以建立 lncRNA 调节表观遗传事件的特征(ELncSig)。ELncSig 是基于独立的淋巴瘤数据集建立的,可以区分不同的生存结果。ELncSig 的功能特征表明,它可以作为免疫微环境的指标,并与独特的突变特征相关。单因素和多因素分析表明,ELncSig 独立于传统的预后因素。新型免疫相关的 ELncSig 对 DLBCL 具有有前途的临床预后价值。