不同病理分期肺腺癌患者血清代谢组学研究

肺癌是当今世界最常见的恶性肿瘤之一,其新发率和死亡率多年来都居于各类癌症之首,其中85%的肺癌都是非小细胞癌,而腺癌又是最常见的非小细胞癌。肺癌的高隐匿性是造成其高死亡率的最主要原因,因此为肺癌的早期诊断和病理分期寻求高效可靠的方法是十分必要的。代谢组学揭示了小分子代谢物的一系列变化,反映了生命活动的最终状态,因此也能直接反映疾病不同发展阶段的病理生理变化。本研究利用核磁共振氢谱(1H-NMR),对在我院就诊的27例不同病理分期的肺腺癌患者和13例健康志愿者进行了血清代谢物分析,运用正交偏最小二乘判别分析(OPLS-DA)对1H-NMR数据进行建模,单变量统计分析对模型进行评价。结果表明肺腺癌患者组的血清中有14种代谢物出现明显差异,其中丙酮酸、丙氨酸、NAC1、乳酸、GPC和甘氨酸比起对照组来有显著上升,而葡萄糖、谷氨酰胺、亮氨酸、异亮氨酸、缬氨酸、丙酮、乙酰乙酸和苏氨酸则显著下降。而在不同分期肺腺癌患者间进行比较后发现,异亮氨酸、乙酰乙酸、NAC1和乳酸的变化与肺腺癌的发展有相关性,可能是肺腺癌早期诊断和分期的潜在生物标志物。

Study on Serum Metabonomics in Patients with Lung Cancer with Different Pathological Stages

Lung cancer is one of the most common malignant tumors in the world.Its new incidence and mortality have been the top among cancers for many years.85%of lung cancers are non-small cell lung cancer(NSCLC),and adenocarcinoma is the most common NSCLC.The high occultity of lung cancer is the most important cause of its high mortality.Therefore,it is necessary to find an efficient and reliable method for early diagnosis and pathological staging of lung cancer.Metabolomics reveals a series of changes in small molecule metabolites that reflect the final state of life activities,as well as directly reflect the pathophysiological changes at different stages of diseases.In this study,nuclear magnetic resonance spectroscopy(1 H-NMR)was used to analyze serum metabolites in 27 patients with different pathological stages of lung adenocarcinoma and 13 healthy volunteers,the1 H-NMR data was modeled by Orthogonal Partial Least Squares Discriminant Analysis(OPLS-DA),using the univariate statistical analysis evaluated the model.The results showed that there were 14 different metabolites in the serum of patients with lung adenocarcinoma.Among them,pyruvate,alanine,NAC1,lactic acid,GPC and glycine showed a significant increase compared with the control group,while glucose,glutamine,leucine,isoleucine,valine,acetone,acetoacetate and threonine were significantly decreased.Compared in patients with different stages of lung adenocarcinoma,the changes of isoleucine,acetoacetate,NAC1 and lactate were correlated with the development of lung adenocarcinoma,which may be potential biomarkers for early diagnosis and staging of lung adenocarcinoma.