Integrative metabonomics as potential method for diagnosis of thyroid malignancy

Abstract

Thyroid nodules can be classified into benign and malignant tumors. However, distinguishing between these two types of tumors can be challenging in clinics. Since malignant nodules require surgical intervention whereas asymptomatic benign tumors do not, there is an urgent need for new techniques that enable accurate diagnosis of malignant thyroid nodules. Here, we used 1H NMR spectroscopy coupled with pattern recognition techniques to analyze the metabonomes of thyroid tissues and their extracts from thyroid lesion patients (n = 53) and their adjacent healthy thyroid tissues (n = 46). We also measured fatty acid compositions using GC−FID/MS techniques as complementary information. We demonstrate that thyroid lesion tissues can be clearly distinguishable from healthy tissues, and malignant tumors can also be distinguished from the benign tumors based on the metabolic profiles, both with high sensitivity and specificity. In addition, we show that thyroid lesions are accompanied with disturbances of multiple metabolic pathways, including alterations in energy metabolism (glycolysis, lipid and TCA cycle), promotions in protein turnover, nucleotide biosynthesis as well as phosphatidylcholine biosynthesis. These findings provide essential information on the metabolic features of thyroid lesions and demonstrate that metabonomics technology can be potentially useful in the rapid and accurate preoperative diagnosis of malignant thyroid nodules.

Alterations in the gut microbiota and metabolite profiles of thyroid carcinoma patients

“…[17][18][19] A previous study investigating TC metabolomics mainly included tissue specimens and serum, and one study investigating TC tissue metabolism found that eight phospholipids, including phosphatidylcholine (PC) (32:0), phosphatidic acid (PA) (36:3) and sphingomyelin (SM) (34:1), were upregulated in TC and could be used to discriminate this malignancy. 29 Another study investigating serum metabolism in TC noted an essential fatty acid (docosahexaenoic acid), a fatty acid (heptadecanoic acid), lyso-phospholipids (LysoPC (18:3)) and other sphingolipid metabolites 31 ; some of these metabolites were also identified in our analysis of TC fecal metabolism. Hence, we hypothesize that gut microbiota dysbiosis is closely correlated with TC development and that lipid metabolism dysregulation might be a crucial factor.…”

“…The interruption of lipid metabolism is related to the onset and severe progression of some types of human cancers, including breast cancer, ovarian cancer and colorectal carcinoma . A previous study investigating TC metabolomics mainly included tissue specimens and serum, and one study investigating TC tissue metabolism found that eight phospholipids, including phosphatidylcholine (PC) (32:0), phosphatidic acid (PA) (36:3) and sphingomyelin (SM) (34:1), were upregulated in TC and could be used to discriminate this malignancy . Another study investigating serum metabolism in TC noted an essential fatty acid (docosahexaenoic acid), a fatty acid (heptadecanoic acid), lyso‐phospholipids (LysoPC (18:3)) and other sphingolipid metabolites; some of these metabolites were also identified in our analysis of TC fecal metabolism.…”

“…23,24,28 In contrast, extensive metabolomics studies have used different samples from TC patients, including thyroid tissue, serum, exhaled breath and urine. [29][30][31][32][33][34] Changes in the concentrations of lipids (linolenic acid and sphingomyelin), galactinol and inosine were identified by TC tissue metabolic profiling. 29,34 Significant changes in serum linolenic acid, phospholipids and gammaaminobutyric acid were observed in TC patients.…”

“…[29][30][31][32][33][34] Changes in the concentrations of lipids (linolenic acid and sphingomyelin), galactinol and inosine were identified by TC tissue metabolic profiling. 29,34 Significant changes in serum linolenic acid, phospholipids and gammaaminobutyric acid were observed in TC patients. 30,31 Phenol and 4-hydroxybutanoic acid levels were changed in the exhaled breath of TC patients.…”

Recent Advances in NMR-Based Metabolomics

“…Similar discrimination was observed in another study that investigated malignant and benign tumors as well as adjacent noncancerous tissue. 118 …”