Laboratory of Tumor Cell Genetics, N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation;
Department of Oncohematology, A.S. Loginov Moscow Clinical Scientific Center, Moscow, Russian Federation.
In Vivo. 2024 Mar-Apr;38(2):657-664. doi: 10.21873/invivo.13486.
BACKGROUND/AIM: Myelodysplastic syndromes (MDS) are clinically heterogeneous hematological malignancies with an increased risk of transformation to acute myeloid leukemia, emphasizing the importance of identifying new diagnostic and prognostic markers. This study sought to investigate the predictive ability of all-trans retinoic acid (ATRA)-dependent nuclear transcription factors RARα and PPARβ/δ gene expression in MDS patients.
Peripheral blood specimens were collected from 49 MDS patients and 15 healthy volunteers. The specimens were further separated in Ficoll density gradient to obtain the mononuclear cells fractions. Gene expression analysis was carried out using quantitative real-time polymerase chain reaction (qRT-PCR) technique.
In the mononuclear cell fractions of MDS patients, RARα expression was increased (p<0.05) and PPARβ/δ expression was decreased (p<0.01) compared to healthy volunteers. When RARα and PPARβ/δ expression was compared in groups of MDS patients with different risks of disease progression, no statistically significant difference was found for RARα expression, while PPARβ/δ expression was significantly lower in the high-risk group of patients compared to the low-risk group (p<0.05). The expression of RARα was significantly associated with overall survival (p<0.05). ROC analysis showed that the expression of PPARβ/δ, rather than RARα expression, could have potential diagnostic value for MDS patients (AUC=0.75, p=0.003 and AUC=0.65, p=0.081, respectively).
RARα and PPARβ/δ genes are putative biomarkers that may be associated with the diagnosis and prognosis of MDS.
背景/目的：骨髓增生异常综合征（MDS）是一种临床异质性血液恶性肿瘤，向急性髓系白血病转化的风险增加，这强调了识别新的诊断和预后标志物的重要性。本研究旨在探讨全反式维甲酸（ATRA）依赖性核转录因子 RARα 和 PPARβ/δ 基因表达在 MDS 患者中的预测能力。
收集了 49 名 MDS 患者和 15 名健康志愿者的外周血标本。进一步使用 Ficoll 密度梯度分离这些标本以获得单核细胞部分。使用定量实时聚合酶链反应（qRT-PCR）技术进行基因表达分析。
与健康志愿者相比，MDS 患者的单核细胞部分 RARα 表达增加（p<0.05），PPARβ/δ 表达减少（p<0.01）。当比较具有不同疾病进展风险的 MDS 患者组中的 RARα 和 PPARβ/δ 表达时，RARα 表达没有统计学上的显著差异，而高危组患者的 PPARβ/δ 表达明显低于低危组（p<0.05）。RARα 的表达与总生存期显著相关（p<0.05）。ROC 分析表明，PPARβ/δ 的表达而非 RARα 的表达可能对 MDS 患者具有潜在的诊断价值（AUC=0.75，p=0.003 和 AUC=0.65，p=0.081）。
RARα 和 PPARβ/δ 基因是可能与 MDS 的诊断和预后相关的潜在生物标志物。
