Li Guangming, Guo Ying, Zhang Yuanyuan
Surgery Base Training, Shanghai Fengxian District Central Hospital, Shanghai, 201499, China.
Department of Hematology, Daqing Oilfield General Hospital, Daqing City, Heilongjiang Province, 163001, China.
Hereditas. 2025 Apr 14;162(1):62. doi: 10.1186/s41065-025-00428-1.
Necroptosis, a recently identified form of programmed cell death involved in the pathogenesis of a variety of tumor and non-tumor diseases. Nevertheless, the function of necroptosis in essential thrombocytosis (ET) remains unclear, which is a classic myeloproliferative tumor.
The role of necroptosis in ET was determined via bioinformatics combined with qRT-PCR analysis of clinical samples. GSE57793 and GSE26049 datasets were recruited to identify necroptosis differentially expressed genes based on differential gene identification, necroptosis gene sets and data machine learning. Enrichment analysis (GSEA) was used to evaluate the gene enrichment signaling pathway of ET, immune infiltration analysis was used to explore the abundance of immune cell infiltration in ET, and the correlation between necroptosis differential genes and immune cell infiltration was studied.
Five necroptosis genes were recognized to be remarkably enriched in the necroptosis pathway, including CHMP1B, FTH1, HSP90AB1, IL1A, and RBCK1. The imbalance of invasion of Th1/Th17 cells was identified in ET, and the differential necroptosis gene was positively correlated with the infiltration of multiple immune cells. There is significant necroptosis in ET, which is enriched in the necrotizing apoptotic pathway, and is associated with immune infiltration.
Necroptosis might drive the progression of ET via stimulating immune infiltration and immune responses. The findings bring new insights into the treatment mechanism and treatment strategy of ET in the future.
坏死性凋亡是最近发现的一种程序性细胞死亡形式,参与多种肿瘤和非肿瘤疾病的发病机制。然而,坏死性凋亡在原发性血小板增多症(ET)中的作用仍不清楚,ET是一种典型的骨髓增殖性肿瘤。
通过生物信息学结合临床样本的qRT-PCR分析来确定坏死性凋亡在ET中的作用。基于差异基因鉴定、坏死性凋亡基因集和数据机器学习,利用GSE57793和GSE26049数据集来识别坏死性凋亡差异表达基因。采用富集分析(GSEA)评估ET的基因富集信号通路,采用免疫浸润分析探索ET中免疫细胞浸润的丰度,并研究坏死性凋亡差异基因与免疫细胞浸润之间的相关性。
五个坏死性凋亡基因被认为在坏死性凋亡途径中显著富集,包括CHMP1B、FTH1、HSP90AB1、IL1A和RBCK1。在ET中发现Th1/Th17细胞侵袭失衡,坏死性凋亡差异基因与多种免疫细胞的浸润呈正相关。ET中存在显著的坏死性凋亡,其在坏死性凋亡途径中富集,并与免疫浸润相关。
坏死性凋亡可能通过刺激免疫浸润和免疫反应来推动ET的进展。这些发现为未来ET的治疗机制和治疗策略带来了新的见解。