Metabolomic Characterization of Ovarian Epithelial Carcinomas by HRMAS-NMR Spectroscopy

Abstract

Objectives. The objectives of the present study are to determine if a metabolomic study by HRMAS-NMR can (i) discriminate between different histological types of epithelial ovarian carcinomas and healthy ovarian tissue, (ii) generate statistical models capable of classifying borderline tumors and (iii) establish a potential relationship with patient's survival or response to chemotherapy. Methods. 36 human epithelial ovarian tumor biopsies and 3 healthy ovarian tissues were studied using 1H HRMAS NMR spectroscopy and multivariate statistical analysis. Results. The results presented in this study demonstrate that the three histological types of epithelial ovarian carcinomas present an effective metabolic pattern difference. Furthermore, a metabolic signature specific of serous (N-acetyl-aspartate) and mucinous (N-acetyl-lysine) carcinomas was found. The statistical models generated in this study are able to predict borderline tumors characterized by an intermediate metabolic pattern similar to the normal ovarian tissue. Finally and importantly, the statistical model of serous carcinomas provided good predictions of both patient's survival rates and the patient's response to chemotherapy. Conclusions. Despite the small number of samples used in this study, the results indicate that metabolomic analysis of intact tissues by HRMAS-NMR is a promising technique which might be applicable to the therapeutic management of patients.

In vivo magnetic resonance spectroscopy for ovarian cancer diagnostics: quantification by the fast Padé transform

“…These assignments are based upon Refs. [50,59,61,62]. Starting from about 0.94 ppm, a doublet and triplet of Leu can be discerned, followed by Iso, Val and glycine (Gly) at ∼1.02, 1.04 and 1.20 ppm, respectively.…”

“…It cannot reliably separate out the noise that corrupts the recorded MRS time signal, such that poor SNR is a major problem when using clinical MR scanners. Yet, there are many MR-observable compounds that characterize malignant versus benign ovarian lesions using in vitro MRS [50,[56][57][58][59][60][61][62].…”

“…An extensive metabolomic assessment using high resolution magic angle spinning (HRMAS) was made of 31 epithelial ovarian carcinomas (22 serous, 4 endometrioid, and 5 mucinous carcinomas), 5 BL ovarian tumors and 3 samples from healthy ovarian tissue [61]. Pattern differences were observed among the malignant subtypes, with NAA being characteristic of serous carcinomas, and N-acetyl-lysine of mucinous carcinomas.…”

Use of 1H and 31P HRMAS to evaluate the relationship between quantitative alterations in metabolite concentrations and tissue features in human brain tumour biopsies

“…The ERETIC signal as a reference for NMR spectra quantification [21] has been already tested in 1 H spectra of human tissues either using either an external electronically generated reference [7,22] or using a synthetic signal [23], but the use of the ERETIC signal has never been tested to evaluate 31 P metabolite concentrations in tissues. The use of ERETIC synthetic signal [23] will be here proposed as a reference to quantify the metabolites in 1 H and also in 31 P spectra of tissues.…”

“…The use of ERETIC synthetic signal [23] will be here proposed as a reference to quantify the metabolites in 1 H and also in 31 P spectra of tissues. The quantitative information of 1 H and 31 P 1D will enable, on one hand confirm the robustness of the ERETIC method comparing the calculated concentration for those metabolites whose signals can be properly integrated in both 1 H and 31 P 1D experiments, and on the other hand, will complete the quantitative information for those metabolites whose signals are challenging to integrate in 1 H and can be properly integrated in 31 P as Phosphoethanolamine and Glycerophosphorylethanolamine.…”