Gas chromatography-mass spectrometry-based untargeted metabolomics reveals metabolic perturbations in medullary thyroid carcinoma

Abstract

Medullary thyroid cancer (MTC) is a rare tumor that arises from parafollicular cells within the thyroid gland. The molecular mechanism underlying MTC has not yet been fully understood. Here, we aimed to perform plasma metabolomics profiling of MTC patients to explore the perturbation of metabolic pathways contributing to MTC tumorigenesis. Plasma samples from 20 MTC patients and 20 healthy subjects were obtained to carry out an untargeted metabolomics by gas chromatography–mass spectrometry. Multivariate and univariate analyses were employed as diagnostic tools via MetaboAnalyst and SIMCA software. A total of 76 features were structurally annotated; among them, 13 metabolites were selected to be differentially expressed in MTC patients compared to controls (P < 0.05). These metabolites were mainly associated with the biosynthesis of unsaturated fatty acids and amino acid metabolisms, mostly leucine, glutamine, and glutamate, tightly responsible for tumor cells' energy production. Moreover, according to the receiver operating characteristic curve analysis, metabolites with the area under the curve (AUC) value up to 0.90, including linoleic acid (AUC = 0.935), linolenic acid (AUC = 0.92), and leucine (AUC = 0.948) could discriminate MTC from healthy individuals. This preliminary work contributes to existing knowledge of MTC metabolism by providing evidence of a distinctive metabolic profile in MTC patients relying on the metabolomics approach.

Faulty Metabolism: A Potential Instigator of an Aggressive Phenotype in Cdk5-dependent Medullary Thyroid Carcinoma

“…Notably, a significant impact on the biosynthesis of unsaturated fatty acids and fatty acid elongation pathways was recognized (Figure 3D and S3B-C). In concordance, impairments in fatty acid metabolism, purine metabolism, and tri-carboxylic acid cycle were reported in MTC patients compared to healthy controls [42]. In summary, our results demonstrated a profile of signaling pathways altered in human tumors and replicated in our mouse models.…”

“…Conversely, the rapidly growing CGRP-p25OE model harbored mutations that predominantly impacted fatty acid metabolism. This finding is supported by a recent study that demonstrated perturbation of fatty acid metabolism in MTC patients compared to healthy controls [42]. In addition, the overlapping mutated genes between CGRP-p25OE mouse and human tumors clustered pathways associated with fatty acid biosynthesis.…”

Exploring the application value of pro‐gastrin‐releasing peptide in the clinical diagnosis and surgical treatment of medullary thyroid carcinoma

“…Furthermore, it is prone to lymph nodes invasion and distant metastasis at an early stage; therefore, its prognosis is relatively poor. The ideal survival period of patients with MTC mainly depends on the time from diagnosis to the application of treatment strategies 6–8 . Therefore, early diagnosis and management of MTC are crucial.…”

“…The ideal survival period of patients with MTC mainly depends on the time from diagnosis to the application of treatment strategies. [6][7][8] Therefore, early diagnosis and management of MTC are crucial.…”

Towards Real-Time Portable Gas Mass Spectroscopy Detection by Multivariate Analysis: a Case Study

“…Three different deep learning algorithms were explored: Single Layer Perceptron, 1-Hidden Layer Multilayer Perceptron, and 5-Hidden Layer Multilayer Perceptron, with the second one giving the better results (63.3% of correct classifications). Jajin et al 22 considered techniques such as Soft Independent Modelling of Class Analogy (SIMCA) and Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) to discriminate between subjects affected by medullary thyroid cancer and healthy ones, using spectra from GC-MS on plasma samples. By using OPLS-DA, an R 2 parameter (coefficient of determination, with maximum 1) value of 0.925 was obtained.…”