原发性肺癌患者血清的代谢组学初步研究*

2016-10-12江建新孙诚谊

贵州医科大学学报 2016年8期

关键词：肺癌血清

田　舍，江建新，张　浩，张　宏，孙诚谊

(贵州医科大学附院，贵州贵阳　550004)

原发性肺癌患者血清的代谢组学初步研究*

田舍，江建新，张浩，张宏，孙诚谊**

(贵州医科大学附院，贵州贵阳550004)

目的：分析原发性肺癌患者血清中小分子代谢产物的改变。方法：利用质子核磁共振(1H NMR)检测18例肺癌(病例组)和同期17例正常体健者(对照组)血清中小分子代谢产物α-葡萄糖、不饱和脂肪酸、肌酐、丙氨酸、谷氨酸盐、丙三醇、苏氨酸、异亮氨基酸、低密度脂蛋白、3-羟丁酸、脂类以及极低密度脂蛋白含量，通过主成分分析法比较两组受检者血清中小分子代谢产物含量的变化。结果：1H NMR图谱能明显区分实验组和对照组血清小分子代谢产物，实验组血清中α-葡萄糖、不饱和脂肪酸及肌酐含量较对照组明显增加，丙氨酸、谷氨酸盐、丙三醇、苏氨酸、异亮氨基酸、低密度脂蛋白、3-羟丁酸、脂类及极低密度脂蛋白较对照组明显减少，差异有统计学意义(P<0.05)。结论：原发性肺癌患者血清中小分子代谢产物与正常体健者存在差异，原发性肺癌患者血清丙氨酸、谷氨酸盐、丙三醇、苏氨酸以及异亮氨基酸可能成为原发性肺癌诊断标志物。

肺肿瘤；代谢组学；质子核磁共振；诊断；生物学标志物

[Abstract]Objective: To analyze the change of small and medium molecular metabolites in blood serum in patients with primary pulmonary carcinoma. Methods:1H NMR was adopted to detect the content of small and medium molecular metabolite, including Alpha-glucose, unsaturated fatty acid, creatinine, alanine, glutamate, glycerol, threonine, isoleucine, low density lipoprotein, 3-hydroxybutyrate, lipids, and very low density lipoprotein, in 18 blood specimens from patients with primary pulmonary carcinoma(experimental group) and 17 specimens from healthy controls(control group). The changes of serum small and medium molecular metabolites in the two groups were analyzed and compared by Partial Least Squares (PLS). Results: MR1H map can clearly distinguish between experimental group and control group in terms of serum small molecule metabolites. In the experimental group, the serum alpha-glucose, unsaturated fatty acid and creatinine content increased significantly compared with those in control group, while alanine, glutamate, glycerol, threonine, isoleucine, low density lipoprotein, 3-hydroxybutyrate, lipids and very low density lipoprotein decreased significantly compared with those in control group, the differences were statistically significant(P<0.05). Conclusion: There exist differences in serum of small molecular metabolites between patients with primary pulmonary carcinoma and normal healthy people. In patients with primary pulmonary carcinoma, serum alanine, glutamate, glycerol, threonine, isoleucine may be the biomarkers in the diagnosis of primary pulmonary carcinoma.

[Key words]lung cancer; metabonomics; proton nuclear magnetic resonance; diagnosis; biomarkers

我国肺癌发病率已达到61.4/10万，由于肺癌起病隐匿，患者对治疗的依从性较差和可普遍运用的检测手段缺乏，确诊的肺癌患者80%已属于晚期，5年生存率<15%[1]。早期诊断和早期治疗是预防肺癌发生和降低死亡率最有效的方法，早期诊断的肺癌患者，5年生存率可达到80%，根治切除后5年生存率可达到35%～50%[2]。因此，寻找一种高特异性、高敏感性的非损伤性的肿瘤诊断标志物应用于临床变得十分必要。代谢组学研究是比较分析健康状态与疾病状态下小分子代谢产物表达的差异，可帮助寻找各种疾病早期诊断的生物标志物，用于疾病预后及治疗效果的评判[3]。基于核磁共振(nuclear magnetic resonance, NMR)的代谢组学方法可以在受检者体内或体外快速、无损伤性地进行代谢物含量的比较分析。本研究采用1HNMR观察原发性肺癌患者血清中小分子代谢产物的变化，分析原发性肺部肿瘤患者血清特征代谢谱，从中筛选代表性小分子标志物，以期为原发性肺癌的早期诊断提供新的分子标记。