HIF-1α在骨髓增生异常综合征患者中表达水平及其与预后的关系

The expression of HIF-1α in myelodysplastic syndrome and its clinical prognostic value

目的:探讨缺氧诱导因子-1α(HIF-1α)在骨髓增生异常综合征(MDS)患者中的表达水平及其与预后的关系。方法 :采用荧光定量PCR(qPCR)法检测48例MDS患者(MDS组)和20例健康捐献者(对照组)骨髓中HIF-1α mRNA的相对表达量,分析HIF-1α的表达与患者预后情况的关系。结果:MDS组HIF-1α mRNA相对表达量明显高于对照组(P<0.001)。23例难治性贫血伴原始细胞增多-1(RAEB1)/RAEB2 MDS患者HIF-1α mRNA相对表达量显著高于25例难治性贫血(RA)/难治性贫血伴环型铁粒幼红细胞增多(RARS)/难治性血细胞减少伴多系发育异常(RCMD)/5q-综合征(5q-)患者(P<0.05)。38例根据国际预后评分系统(IPSS)进行分组,其中18例IPSS≥1.5分患者HIF-1α mRNA相对表达量显著高于20例IPSS<1.5分患者(P<0.05),MDS患者HIF-1α mRNA相对表达量与IPSS预后评分呈正相关关系(r=0.54,P<0.001)。免疫荧光原位杂交(FISH)检测及染色体异常组患者HIF-1α mRNA相对表达量均显著高于正常组(均P<0.05),MDS患者HIF-1α mRNA表达水平与染色体核型预后呈正相关关系(r=0.62,P<0.001)。结论:HIF-1α在MDS患者中呈高表达,且与染色体核型异常有关,可能是MDS患者预后不良的因素之一。

Objective：To investigate the expression of hypoxia-inducible factor-1α（HIF-1α） in patients with myelodysplastic syndrome （MDS） and its clinical prognostic value. Methods.. The mRNA expression of HIF-1α in bone marrow from 48 MDS patients and 20 healthy donates were detected by qPCR, and the relationship between the expression of HIF-1α and the clinical characteristics was analyzed. Results： The mRNA expression of HIF-1 α in MDS patients was significantly higher than that in controls （ P 〈0. 001）. The mRNA expression of HIF-1α in 23 cases with refractory anemia （RA） with excess blasts （RAEB） was obviously higher than 9.5 cases with RA, RA with ring sideroblasts （RARS）, RA with multiple dysplasia （RCMD） and 5q syndrome （ P 〈0.05）. According to International Prognostic Scoring System （IPSS） score, of 38 patients with MDS, the expression of HIF-1α mRNA was higher in 18 patients with IPSS score ≥1.5, compared to those with IPSS score 〈1.5 （ P 〈0.05）. Spearman correlation analysis showed that the expression of HIF-1α in MDS patients was positively correlated with IPSS prognosis score （ r =0.54, P 〈0. 001）. Fluorescence in situ hybridization （FISH） and chromosome karyotype analysis showed that the mRNA expression of HIF-1α in chromosomal-abnormal group was significantly higher than that in chromosome-normal group （ P 〈0.05）. The mRNA expression of HIF-1α in MDS patients was positively correlated with chromosome karyotype prognosis （ r =-0.62, P 〈0. 001）. Conclusion： High expression of HIF-1α mRNA in MDS patients was associated with chromosome karyotype abnormality, which may be one of the poor prognostic factors for MDS.