Taha Safa, Abdulwahab Hawra, Aljishi Muna, Sultan Ameera, Bakhiet Moiz, Spicuglia Salvatore, Belhocine Mohamed
Department of Molecular Medicine, Princess Al Jawhara Center for Molecular Medicine, Genetics and Inherited Diseases, College of Medicine and Health Sciences, Arabian Gulf University, Manama P.O. Box 26671, Bahrain.
Equipe Labélisée Ligue Contre le Cancer, Aix-Marseille University, INSERM, TAGC, UMR1090, 13288 Marseille, France.
Int J Mol Sci. 2025 Jun 30;26(13):6338. doi: 10.3390/ijms26136338.
Sickle cell disease (SCD) is the most common hemoglobinopathy, caused by a mutation in the β-globin gene of hemoglobin. It predisposes patients to painful Vaso-occlusive crises (VOC) and multi-organ dysfunctions. The disease exhibits significant phenotypic variability, making it challenging to predict severity and outcomes. This study aimed to characterize the whole blood gene expression profile of Bahraini SCD patients, identifying differentially expressed genes during steady-state ( = 10) and VOC ( = 10) compared to healthy controls ( = 8). Analysis revealed 2073 and 3363 dysregulated genes during steady-state and VOC, respectively, compared to controls, with 1078 genes differentially expressed during VOC versus steady-state. Gene Ontology (GO) enrichment analysis highlighted significant deregulation in immune and hematopoietic pathways, including down-regulation of critical genes for immune modulation and hematopoietic balance. Notably, the transcription factor RUNX3, involved in immune cell differentiation and inflammation, was among the 668 down-regulated genes. RUNX3 was four-fold down-regulated in microarray analysis, three-fold in PCR, and showed a mean protein concentration of 11.13 pg/mL during VOC compared to 457.93 pg/mL during steady-state ( < 0.01). These findings suggest that RUNX3 may serve as a potential biomarker for VOC. Future large-scale validation, additional proteomic studies, and functional investigations are recommended to confirm its clinical utility and significance.
镰状细胞病（SCD）是最常见的血红蛋白病，由血红蛋白β-珠蛋白基因突变引起。它使患者易患疼痛性血管闭塞危象（VOC）和多器官功能障碍。该疾病表现出显著的表型变异性，使得预测严重程度和预后具有挑战性。本研究旨在描述巴林SCD患者的全血基因表达谱，确定与健康对照（n = 8）相比，稳态期（n = 10）和VOC期（n = 10）差异表达的基因。分析显示，与对照组相比，稳态期和VOC期分别有2073个和3363个基因表达失调，其中1078个基因在VOC期与稳态期差异表达。基因本体（GO）富集分析突出了免疫和造血途径中的显著失调，包括免疫调节和造血平衡关键基因的下调。值得注意的是，参与免疫细胞分化和炎症的转录因子RUNX3是668个下调基因之一。在微阵列分析中，RUNX3下调了四倍，在PCR中下调了三倍，与稳态期的457.93 pg/mL相比，VOC期的平均蛋白浓度为11.13 pg/mL（P < 0.01）。这些发现表明，RUNX3可能作为VOC的潜在生物标志物。建议未来进行大规模验证、额外的蛋白质组学研究和功能研究，以证实其临床实用性和意义。
