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.
Highlights
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
A substantial overlap between the different tumor grades and the disease stages is seen in the PC1-PC2 projection plane, the majority of the G1 and G2 tumors were assigned the negative PC1 scores, while the G2 and G3 tumors were characterized by the positive PC1 scores (Fig. 3a)
The metabolic profiles of the endometrial cancers were found to be dysregulated as compared to the healthy endometrium and the metabolic diversity between the EC histological grades and stages was characterized
Summary
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. ECs are assigned the FIGO (International Federation of Gynaecology and Obstetrics) grades based on the degree of glandular d ifferentiation[6,7], in one-third or more cases the pathologic accuracy of the tumor grade (mainly in grade 3 endometrioid and serous cancers) is occasionally low due to a poor diagnostic reproducibility[2] This dualistic classification system remains the gold standard, a new classification by The Cancer Genome Atlas (TCGA) Consortium, based on the molecular features, is starting to be integrated into a clinical practice[8]. In EC the biomarkers of the mentioned processes are useful for cancer detection or treatment monitoring and can be linked to specific histological or molecular subtypes of EC, to explore the intra-tumor heterogeneity[16,17,18,19], and to direct the targeted treatments or to predict the EC o utcome[13,20]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call