靶标代谢组学案例分析

领域：多组学/蛋白质组/代谢组/脂质组    资料类型：其他资料   

乳头状甲状腺肿瘤诊断和治疗的潜在生物标志物

研究对象：

分析检测平台：GC-TOF／MS和UHPLC-QqQ-MS（BIOTREE）

期刊：Tumor Biology

影响因子：2.926

发表时间：2016

摘要：

Papillary thyroid carcinoma (PTC) is the most common pathological type of thyroid cancer. Our study was to construct a tissue-targeted metabolomics analysis method based on untargeted and targeted metabolic multi-platforms to identify a comprehensive PTC metabolic network in clinical samples. We applied untargeted gas chromatography-time of-flight mass spectrometry (GC-TOF-MS) for preliminary screening of potential biomarkers. With diagnostic models constructed using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA), 45 differentially abundant metabolites with a variable importance in the projection (VIP) value greater than 1 and a P value less than 0.05 were identified, and we show that our approach was able to discriminate PTC tissues from healthy tissues. We then performed validation experiments based on targeted GCTOF-MS combined with ultra-high-performance liquid chromatography-triple-quadrupole mass spectrometry (UHPLC-QqQ-MS) through constructing linear standard curves of analytes. Ultimately, galactinol, melibiose, and melatonin were validated as significantly altered metabolites (p 0.05). These three metabolites were defined as a combinatorial biomarker to assist needle biopsy for PTC diagnosis as demonstrated by receiver operating characteristic (ROC) curve analysis, which revealed an area under the ROC curve (AUC) value of 0.96. Based on the metabolite enrichment analysis results, the galactose metabolism pathway was regarded as an important factor influencing PTC development by affecting energy metabolism. Alpha-galactosidase (GLA) was considered to be a potential target for PTC therapy.

研究背景：

甲状腺肿瘤的发病率逐年升高，通过早期的诊断和治疗可有效降低其复发率和致死率。目前甲状腺肿瘤主要通过超声和超声介导的穿刺活体切片（FNAB）进行诊断，但其特异性等仍有待提高。肿瘤生物标志物可与FNAB方法结合使用，以更准确地进行恶性肿瘤诊断。乳突状甲状腺肿瘤（PTC）是常见的恶性甲状腺肿瘤的亚型之一。如整合目前代谢组学研究中的非靶向（GC-TOF-MS）和靶向（UHPLC-QqQ-MS）两种研究平台可更加高效和可靠地进行潜在生物标志物的筛选。