文章：

利用基因共表达网络方法识别与儿童T细胞急性淋巴细胞白血病复发相关的候选驱动基因

Identifying Candidate Gene Drivers Associated with Relapse in Pediatric T-Cell Acute Lymphoblastic Leukemia Using a Gene Co-Expression Network Approach

原文发布日期：25 April 2024

DOI: 10.3390/cancers16091667

类型: Article

开放获取: 是

英文摘要：

Pediatric T-cell Acute Lymphoblastic Leukemia (T-ALL) relapses are still associated with a dismal outcome, justifying the search for new therapeutic targets and relapse biomarkers. Using single-cell RNA sequencing (scRNAseq) data from three paired samples of pediatric T-ALL at diagnosis and relapse, we first conducted a high-dimensional weighted gene co-expression network analysis (hdWGCNA). This analysis highlighted several gene co-expression networks (GCNs) and identified relapse-associated hub genes, which are considered potential driver genes. Shared relapse-expressed genes were found to be related to antigen presentation (HLA, B2M), cytoskeleton remodeling (TUBB, TUBA1B), translation (ribosomal proteins, EIF1, EEF1B2), immune responses (MIF, EMP3), stress responses (UBC, HSP90AB1/AA1), metabolism (FTH1, NME1/2, ARCL4C), and transcriptional remodeling (NF-κB family genes, FOS-JUN, KLF2, or KLF6). We then utilized sparse partial least squares discriminant analysis to select from a pool of 481 unique leukemic hub genes, which are the genes most discriminant between diagnosis and relapse states (comprising 44, 35, and 31 genes, respectively, for each patient). Applying a Cox regression method to these patient-specific genes, along with transcriptomic and clinical data from the TARGET-ALL AALL0434 cohort, we generated three model gene signatures that efficiently identified relapsed patients within the cohort. Overall, our approach identified new potential relapse-associated genes and proposed three model gene signatures associated with lower survival rates for high-score patients.

摘要翻译： 

儿童T细胞急性淋巴细胞白血病（T-ALL）的复发仍与不良预后相关，这促使我们寻找新的治疗靶点和复发生物标志物。基于三对儿童T-ALL患者在初诊与复发期的单细胞RNA测序（scRNAseq）数据，我们首先进行了高维加权基因共表达网络分析（hdWGCNA）。该分析揭示了多个基因共表达网络（GCNs），并识别出与复发相关的枢纽基因，这些基因被认为是潜在的驱动基因。研究发现，复发期共同表达的基因与抗原呈递（HLA、B2M）、细胞骨架重塑（TUBB、TUBA1B）、翻译过程（核糖体蛋白、EIF1、EEF1B2）、免疫应答（MIF、EMP3）、应激反应（UBC、HSP90AB1/AA1）、代谢（FTH1、NME1/2、ARCL4C）以及转录重塑（NF-κB家族基因、FOS-JUN、KLF2或KLF6）相关。随后，我们采用稀疏偏最小二乘判别分析，从481个独特的白血病枢纽基因池中筛选出最能区分初诊与复发状态的基因（每位患者分别对应44、35和31个基因）。结合TARGET-ALL AALL0434队列的转录组与临床数据，我们通过Cox回归方法对这些患者特异性基因进行分析，构建了三个模型基因特征，能有效识别该队列中的复发患者。总体而言，我们的研究发现了新的潜在复发相关基因，并提出了三个模型基因特征，这些特征在高评分患者中与较低的生存率相关。

原文链接：

Identifying Candidate Gene Drivers Associated with Relapse in Pediatric T-Cell Acute Lymphoblastic Leukemia Using a Gene Co-Expression Network Approach