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非靶向¹H-NMR代谢组学方法揭示甲状腺乳头状癌患者基于血清的代谢改变

Serum-based metabolic alterations in patients with papillary thyroid carcinoma unveiled by non-targeted 1H-NMR metabolomics approach.

作者信息

Farrokhi Yekta Reyhaneh, Rezaei Tavirani Mostafa, Arefi Oskouie Afsaneh, Mohajeri-Tehrani Mohammad Reza, Soroush Ahmad Reza, Akbarzadeh Baghban Alireza

机构信息

Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Basic Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Basic Med Sci. 2018 Nov;21(11):1140-1147. doi: 10.22038/IJBMS.2018.30375.7323.

Abstract

OBJECTIVES

As the most prevalent endocrine system malignancy, papillary thyroid carcinoma had a very fast rising incidence in recent years for unknown reasons besides the fact that the current methods in thyroid cancer diagnosis still hold some limitations. Therefore, the aim of this study was to improve the potential molecular markers for diagnosis of benign and malignant thyroid nodules to prevent unnecessary surgeries for benign tumors.

MATERIALS AND METHODS

In this study, 1H-NMR metabolomics platform was used to seek the discriminating serum metabolites in malignant papillary thyroid carcinoma (PTC) compared to benign multinodular goiter (MNG) and healthy subjects and also to better understand the disease mechanisms using bioinformatics analysis. Multivariate statistical analysis showed that PTC and MNG samples could be successfully discriminated in PCA and OPLS-DA score plots.

RESULTS

Significant metabolites that differentiated malignant and benign thyroid lesions included citrate, acetylcarnitine, glutamine, homoserine, glutathione, kynurenine, nicotinic acid, hippurate, tyrosine, tryptophan, β-alanine, and xanthine. The significant metabolites in the PTC group compared to healthy subjects also included scyllo- and myo-inositol, tryptophan, propionate, lactate, homocysteine, 3-methyl glutaric acid, asparagine, aspartate, choline, and acetamide. The metabolite sets enrichment analysis demonstrated that aspartate metabolism and urea cycle were the most important pathways in papillary thyroid cancer progression.

CONCLUSION

The study results demonstrated that serum metabolic fingerprinting could serve as a viable method for differentiating various thyroid lesions and for proposing novel potential markers for thyroid cancers. Obviously, further studies are needed for the validation of the results.

摘要

目的

作为最常见的内分泌系统恶性肿瘤,近年来甲状腺乳头状癌的发病率迅速上升,原因不明,此外甲状腺癌诊断的现有方法仍存在一些局限性。因此,本研究的目的是改进诊断甲状腺良恶性结节的潜在分子标志物,以避免对良性肿瘤进行不必要的手术。

材料与方法

在本研究中,采用1H-NMR代谢组学平台寻找与良性结节性甲状腺肿(MNG)和健康受试者相比,恶性甲状腺乳头状癌(PTC)中具有鉴别意义的血清代谢物,并通过生物信息学分析更好地了解疾病机制。多变量统计分析表明,在主成分分析(PCA)和正交偏最小二乘法判别分析(OPLS-DA)得分图中,PTC和MNG样本能够成功区分。

结果

区分恶性和良性甲状腺病变的显著代谢物包括柠檬酸、乙酰肉碱、谷氨酰胺、高丝氨酸、谷胱甘肽、犬尿氨酸、烟酸、马尿酸盐、酪氨酸、色氨酸、β-丙氨酸和黄嘌呤。与健康受试者相比,PTC组中的显著代谢物还包括 scyllo-肌醇和肌醇、色氨酸、丙酸盐、乳酸、同型半胱氨酸、3-甲基戊二酸、天冬酰胺、天冬氨酸、胆碱和乙酰胺。代谢物集富集分析表明,天冬氨酸代谢和尿素循环是甲状腺乳头状癌进展中最重要的途径。

结论

研究结果表明,血清代谢指纹图谱可作为区分各种甲状腺病变和提出甲状腺癌新的潜在标志物的可行方法。显然,需要进一步研究来验证这些结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d56c/6251387/fba5cc61a2af/IJBMS-21-1140-g001.jpg

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