摘要: 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 (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.
四、亮点和展望 l 非靶标代谢组学实验之后用靶标实验对标志性差异物进行精确定量,为建立生物标志物提供了更加坚实的基础; l 通过靶标实验更精确地定位癌细胞中发生变化的代谢通路,为后续研究提供更可靠的线索 l 展望:针对精确定量得到的生物标志物可通过大样本进行验证和推进 l 展望:针对乳糖代谢途径进行多角度研究,研究其细致的调节机制