GDF15在铁过载骨髓增生异常综合征患者中的表达

Expression of GDF15 in iron overload myelodysplastic syndrome patients

目的:检测骨髓增生异常综合征(myelodysplastic syndrome,MDS)患者骨髓中生长分化因子15(GDF15)的表达情况和铁调素、促红细胞生成素(EPO)、血清铁蛋白(SF)水平及心脏、肝脏MRI T2*数值,探讨GDF15表达在MDS铁过载中的意义。方法:采用荧光定量PCR测定GDF15 mRNA表达水平,利用双抗体夹心ELISA法测定铁调素水平,并对24例患者进行MRI T2*检测,得到心脏及肝脏MRI T2*数值,换算为心铁、肝铁浓度。结果:MDS患者铁过载组中的GDF15表达量显著高于铁正常组(P<0.001),2组间的铁调素水平也存在显著差异(P=0.001)。MDS铁过载组患者的GDF15表达与铁调素水平间有相关性(r=0.663,P<0.001),而铁正常组中两者间则未见相关性(r=0.199,P=0.275)。EPO与铁调素间在铁过载组及正常组中均无相关性(r=0.301,P=0.697;r=2.433,P=0.805),而铁调素在国际预后评分系统(IPSS)及MDS的WHO分型预后积分系统(WPSS)高危与低危组间的差异均有统计学意义(P=0.015和P=0.005),GDF15、SF在WPSS高危组与低危组间亦呈现显著差异(P=0.037,P=0.028),IPSS高危组与低危组间的GDF15、SF、EPO水平则均无统计学差异。结论:GDF15表达水平与MDS疾病本身间无相关性,但在铁过载的前提下,GDF15表达升高,从而可能发挥了抑制铁调素生成的作用。

Objective To determine the growth differential factor 15 （GDF15） , hepcidin, cardiac and liver T2＊ values in myelodysplastic syndrome （MDS） patients and define the significance of GDF15 in iron overload MDS. Methods A total of sixty-four MDS patients were enrolled in this study. Real-time quantitative polymerase chain reaction was performed to determine the gene expression of GDF15. ELISA was used to measure serum hepcidin. Twenty-four MDS patients were measured for cardiac and liver iron deposition levels through MRI T2^＊ examination, HIC and LIC were transformed from cardiac T2^＊ and liver T2^＊. Results The gene expression of GDF15 in iron overload （IO） group in MDS patients was higher than iron normal group （P〈0.001）, so did serum hepcidin （P=0.001）. GDF15 was correlated with hepcidin in IO group （r=0.663,P〈0.001）, but not in iron normal group （r=O.199,P=0.275）. EPO had no correlation with GDF15 in both IO group and iron normal group （P=O.O15 and P=0.005）. Serum hepcidin had a statistical difference between high-risk group and low-risk group stratified according to IPSS （P=0.015） and WPSS （P=0.005）, respectively. There was a statistical difference of GDF15 between high-risk group and low-risk group stratified according to WPSS （P= 0.037）. But GDF15, SF and EPO did not display the same result between high risk group and low risk group stratified according to IPSS. Conclusions GDF15 has no relation with MDS disease itself. However, the expression of GDF15 will elevate in iron overload circumstance, thereby suppressing hepcidin.