Hematology Center, The First Affiliated Hospital of Xinjiang Medical University, No. 137 Liyushan South Road, Urumqi, 830054, Xinjiang, China.
Sci Rep. 2024 Sep 28;14(1):22443. doi: 10.1038/s41598-024-73325-8.
Chronic lymphocytic leukemia (CLL) presents with heterogeneous clinical outcomes, suggesting varied underlying pathogenic mechanisms. This study aims to elucidate the impact of T follicular helper (Tfh) cells on CLL progression and prognosis. Gene expression profile data for CLL were collected from GSE22762 and GSE39671 datasets. Patients were divided into high and low groups using Tfh levels using the optimal cutoff value based on overall survival (OS) and time-to-first treatment (TTFT). Differential expression analysis was performed between these groups, followed by co-expression network analysis and single-sample Gene Set Enrichment Analysis (ssGSEA). Marker genes of Tfh cells were used to construct prognostic models. Additionally, 40 CLL patients were recruited and categorized based on median Tfh levels. Marker gene expression was assessed using RT-qPCR and Western Blot, and immune cell levels were determined through flow cytometry. The high group showed better prognosis compared to the low group. Among the 1121 differentially expressed genes identified, five co-expression networks were constructed, with the turquoise module showing the highest correlation with Tfh cells. Genes within this module significantly participate in cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, and natural killer cell mediated cytotoxicity. Tfh cells were significantly negatively correlated with activated B cells and positively correlated with Tregs. The Random Survival Forest (RSF) model identified 10 marker genes, and further analysis using Lasso regression and nomogram selected CLEC4A, RAE1, CD84, and PRDX1 as prognostic markers. In the high group, levels of CLEC4A and RAE1 were higher than in the low group, whereas CD84 and PRDX1 were lower. Flow cytometry revealed that the level of activated B cells in the high Tfh group was significantly lower than in the low Tfh group, while the level of Tregs is significantly higher in the high Tfh group. This study seeks to contribute to a more detailed understanding of the pathogenesis of CLL, delving into the prognostic significance of Tfh.
慢性淋巴细胞白血病（CLL）表现出异质性的临床结局，提示存在不同的潜在发病机制。本研究旨在阐明滤泡辅助 T 细胞（Tfh）对 CLL 进展和预后的影响。从 GSE22762 和 GSE39671 数据集收集 CLL 的基因表达谱数据。根据总生存期（OS）和首次治疗时间（TTFT），使用 Tfh 水平的最佳截止值将患者分为高和低两组。在这些组之间进行差异表达分析，然后进行共表达网络分析和单样本基因集富集分析（ssGSEA）。使用 Tfh 细胞的标记基因构建预后模型。此外，招募了 40 名 CLL 患者，并根据中位数 Tfh 水平进行分类。使用 RT-qPCR 和 Western Blot 评估标记基因的表达，通过流式细胞术测定免疫细胞水平。高组的预后明显优于低组。在鉴定的 1121 个差异表达基因中，构建了 5 个共表达网络，其中绿松石模块与 Tfh 细胞的相关性最高。该模块中的基因显著参与细胞因子-细胞因子受体相互作用、PI3K-Akt 信号通路和自然杀伤细胞介导的细胞毒性。Tfh 细胞与活化 B 细胞呈显著负相关，与 Tregs 呈显著正相关。随机生存森林（RSF）模型鉴定了 10 个标记基因，进一步使用 Lasso 回归和列线图分析选择 CLEC4A、RAE1、CD84 和 PRDX1 作为预后标志物。在高组中，CLEC4A 和 RAE1 的水平高于低组，而 CD84 和 PRDX1 的水平低于低组。流式细胞术显示，高 Tfh 组活化 B 细胞的水平明显低于低 Tfh 组，而高 Tfh 组 Tregs 的水平明显更高。本研究旨在深入了解 CLL 的发病机制，探讨 Tfh 的预后意义。
