Grading of endometrial cancer using 1H HR-MAS NMR-based metabolomics

Abstract

The tissue metabolomic characteristics associated with endometrial cancer (EC) at different grades were studied using high resolution (400 MHz) magic angle spinning (HR-MAS) proton spectroscopy. The metabolic profiles were obtained from 64 patients (14 with grade 1 (G1), 33 with grade 2 (G2) and 17 with grade 3 (G3) tumors) and compared with the profile acquired from 10 patients with the benign disorders. OPLS-DA revealed increased valine, isoleucine, leucine, hypotaurine, serine, lysine, ethanolamine, choline and decreased creatine, creatinine, glutathione, ascorbate, glutamate, phosphoethanolamine and scyllo-inositol in all EC grades in reference to the non-transformed tissue. The increased levels of taurine was additionally detected in the G1 and G2 tumors in comparison to the control tissue, while the elevated glycine, N-acetyl compound and lactate—in the G1 and G3 tumors. The metabolic features typical for the G1 tumors are the increased dimethyl sulfone, phosphocholine, and decreased glycerophosphocholine and glutamine levels, while the decreased myo-inositol level is characteristic for the G2 and G3 tumors. The elevated 3-hydroxybutyrate, alanine and betaine levels were observed in the G3 tumors. The differences between the grade G1 and G3 malignances were mainly related to the perturbations of phosphoethanolamine and phosphocholine biosynthesis, inositol, betaine, serine and glycine metabolism. The statistical significance of the OPLS-DA modeling was also verified by an univariate analysis. HR-MAS NMR based metabolomics provides an useful insight into the metabolic reprogramming in endometrial cancer.

Endometrial cancer diagnostic and prognostic algorithms based on proteomics, metabolomics, and clinical data: a systematic review

“…( 152 ) employed NMR to analyse tissues from 17 ECs and 18 control patients, and reported a number of candidate metabolite biomarkers e.g., lactate, alanina, phenylalanine and ratios glutamate/glutamine/methionine and leucine/isoleucine with AUCs up to 0.88 ( Supplementary Table S8 ). A recent non-targeted NMR analysis on 64 EC tissue (patients with different grades of disease) and 10 tissues from patients with benign uterine diseases, identified using OPLS-DA the levels of a number of metabolites differentiating the patient groups ( 151 ). The concentrations of dimethylsulfone and phosphocholine were higher whereas the concentrations of glycerophosphocholine and glutamine were lower in low grade EC.…”

The emerging roles of PHOSPHO1 and its regulated phospholipid homeostasis in metabolic disorders

“…Endometrial cancer was correlated with a diversity of metabolic disorders, such as obesity, hypertension, and diabetes ( Kyo and Nakayama, 2020 ). The increased level of phosphocholine is the metabolic character of the well-differentiated and low-grade endometrial cancer type ( Skorupa et al, 2021 ). The ratio of o-phosphocholine to UDP-N-acetylglucosamine within pancreatic β-cells is a probable indicator of glucotoxicity, lipotoxicity, glucolipotoxicity, and metabolic imbalances associated with T2D ( Yousf et al, 2019 ).…”

Leaf tissue metabolomics fingerprinting of Citronella gongonha Mart. by 1H HR-MAS NMR

“…HR-MAS NMR is an emerged hybrid tool designed with the liquid- and solid-state skills, has a decisive role in tracking metabolites directly in composite semisolid tissues in negligible amount that made tissue metabolomics attractive 3 , 17 , 19 , 20 . In recent years, 1 H HR-MAS NMR-based tissue metabolomics has greatly assisted to tracing environmental perturbations on the plant metabolome 3 , 17 .…”

“…Of note, 1 H HR-MAS NMR capably spots molecules at the solvent interface via solution-state experiment, whilst the unsolicited atomic interactions are averaged by solid-state MAS technique 22 . 1 H HR-MAS NMR-based tissue metabolomics provides enhanced advantages, involving molecular integrity, hence fingerprinting by this tool has satisfied researchers, dealing with diverse objectives 3 , 17 , 18 , 20 , 23 .…”