title: Metabolomics of papillary thyroid carcinoma tissues: potential biomarkers for diagnosis and promising targets for therapy.
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 GC-TOF-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.
authors.affiliation: Department of Breast and Thyroid Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Xingchen
authors.initials: X
authors.lastname: Shang
authors.affiliation: Department of Emergency, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Department of Breast and Thyroid Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China. sddxtxs@126.com.
authors.forename: Xingsong
authors.initials: X
authors.lastname: Tian
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000378:metabolism*; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism*; D002291:Carcinoma, Papillary; D002849:Chromatography, Gas; D002853:Chromatography, Liquid; D016002:Discriminant Analysis; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D025341:Principal Component Analysis; D012372:ROC Curve; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarker; Metabolism pathway; Papillary thyroid cancer (PTC); Targeted metabolomics; Untargeted metabolomics