乙醛脱氢酶1A 3和巢蛋白表达与原发性星形胶质细胞瘤患者预后的关系

The relationship of aldehyde dehydrogenase 1A3 and Nestin expressions to the prognosis of primary astrocytomas

目的 探讨乙醛脱氢酶1A 3（ALDH1A3）和巢蛋白（Nestin）的表达与原发性星形胶质细胞瘤患者预后的关系及对可能机制的初步探讨.方法 标本均来自于2006年1月至2012年1月在首都医科大学附属北京天坛医院神经外科行手术治疗的原发星形胶质细胞瘤患者,共130例.采用全基因组mRNA测序获得肿瘤干细胞标志物CD133、ALDH1A3、Nestin mRNA的表达,采用异柠檬酸脱氢酶1（IDH1）焦磷酸测序获得IDH1突变类型.按照基因表达值从高到低,前65例为此基因高表达组,后65例为低表达组,其中ALDH1A3和Nestin均高表达者为A组（32例）,ALDH1A3高表达＋ Nestin低表达或ALDH1A3低表达＋Nestin高表达者为B组（66例）,ALDH1A3和Nestin均低表达者为C组（32例）.分析3种肿瘤干细胞标志物的表达与预后的关系及各组IDH1突变类型对预后的影响.结果 （1） ALDH1A3高、低表达组患者的中位生存时间分别为432 d、1 131 d,Nestin高、低表达组患者的中位生存时间分别为423 d、1 074 d,差异均有统计学意义（均P＜0.001）;CD133高、低表达组患者的中位生存时间分别为720 d、965 d,差异无统计学意义（P =0.273）.（2）A、B组的中位生存时间分别为333 d、720 d;C组的生存时间最长,至末次随访有＞50％的患者生存.3组比较差异有统计学意义（P＜0.001）.（3）A、B、C组IDH1野生型分别占100.0％ （32/32）、75.8％（50/66）、21.9％（7/32） （P＜0.001）.B组IDH1野生型和突变型者的中位生存期分别为514 d、1 374 d（P=0.028）,C组IDH1野生型者的中位生存期为660 d,突变型者至末次随访有＞50％的患者存活（P＜0.001）.结论 在原发性星形胶质细胞瘤患者中,肿瘤干细胞标志物ALDH1 A3、Nestin的表达可能与预后有关;IDH1的突变类型可能参与对患者预后的影响.

Objective To explore the relationship of cancer stem cell markers to the prognosis of primary astrocytomas and its possible mechanisms.Methods A total of 130 cases of primary astrocytomas were admitted to Department of Neurosurgery,Beijing Tiantan Hospital,Capital Medical University and underwent surgical operations from January 2012 to January 2016 whose data were retrospectively analyzed.The expressions of cancer stem cell markers CD133,aldehyde dehydrogenase 1A3 （ALDH1A3） and Nestin and IDH1 mutation were obtained through the whole transcriptome sequencing and isocitrate dehydrogenase 1 （IDH1） pyrophosphate sequencing.According to the genes expression levels from high to low,the top 65 cases were defined as high gene expression groups,and the last 65 cases were defined as low expression groups.Among them,patients with both ALDH1A3 and Nestin high expressions were termed as group A （32 cases）,ALDH1A3 high expression/Nestin low expression and ALDH1A3 low expression/Nestin high expression were defined as group B （66 cases）,and group C （32 cases） consisted of those with ALDH1A3 and Nestin both low expression.The relationship between the expressions of the 3 markers and patients＆#39;prognosis and the effect of IDH1 mutation on prognosis in different groups were analyzed.Results （1）The median survival time of the patients with ALDH1A3 high and low expression was 432 d and 1 131 d,respectively.The median survival time of Nestin high expression group and Nestin low expression group was 423 d and 1 074 d,respectively.The differences were statistically significant （all P 〈0.001）.The median survival time of the patients with ALDH1A3 high and low expression was 720 d and 965 d,respectively （P =0.273）.（2） Group A and B had median survival time of 333 d and 720 d,respectively.Group C showed the best prognosis.More than 50% of the patients survived the last follow-up.The differences were statistically significant （P〈0.001）.（3） The proportions of IDH1 wild type in group A,B and C were 100.0% （32/32）,75.8 % （50/66） and 21.9% （7/32）,respectively （P 〈 0.001）.The median survival time of IDH1 wild type and mutation type in Group B were 514 d and 1 374 d,respectively （P =0.028）.In Group C,patients with IDH1 wild type had a median survival time of 660 d.IDH1 mutation type group had better prognosis and more than 50% of the patients survived the last follow-up （P 〈0.001）.Conclusion The expressions of cancer stem cell markers ALDH1A3 and Nestin are related to the prognosis of primary astrocytomas,in which the IDH1 mutation may be involved.