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[分享] 靶标代谢组学案例分析

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发表于 2017-3-16 17:12:27 | 显示全部楼层 |阅读模式

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[ 本帖最后由 shbiotree 于 2017-3-16 17:17 编辑 ]\n\n乳头状甲状腺肿瘤诊断和治疗的潜在生物标志物
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分析检测平台:GC-TOF/MS和UHPLC-QqQ-MS(BIOTREE)
& i# s9 R1 G8 I( l* W/ _% ^期刊:Tumor Biology
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发表时间:2016
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摘要:% P. G7 p5 |2 l/ u
Abstract 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
' ~4 r2 y3 d( G: t  x(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.! M9 l: D3 Y% Y9 Z
研究背景:! @- u5 s/ F' B6 A( i; ^) G
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。; B$ J: {1 h. \4 A
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阅读文献下载地址:
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Shang X, Zhong X, Tian X. Metabolomics of papillary thyroid carcinoma tissues: potential biomarkers for diagnosis and promising targets for therapy. Tumor Biology, 2016, 37(8):1-13.

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