Diagnosis of Early Stage Ovarian Cancer by¹H NMR Metabonomics of Serum Explored by Use of a Microflow NMR Probe

Abstract

We show that 1 H NMR based metabonomics of serum allows the diagnosis of early stage I/II epithelial ovarian cancer (EOC) required for successful treatment. Because patient specimens are highly precious, we conducted an exploratory study using a micro-flow probe requiring only 20 μL serum. By use of logistic regression on principal components (PCs) of the NMR profiles, we built a 4-variable model for early stage EOC prediction (training set: 69 EOC specimens, 84 healthy controls; test set: 40 EOC, 44 controls) with operating characteristics estimated for the test set at 80% specificity [95% confidence interval (CI): 65% to 90%], 63% sensitivity (95% CI: 46% to 77%), and an area under the Receiver Operator Characteristic Curve (AUC) of 0.796. Independent validation (50 EOC, 50 controls) of the model yielded 95% specificity (95% CI: 86% to 99.5%), 68% sensitivity (95% CI: 53% to 80%) and an AUC of 0.949. A test on cancer type specificity showed that women diseased with renal cell carcinoma were not incorrectly diagnosed with EOC, indicating that metabonomics bears significant potential for cancer type-specific diagnosis. Our model can potentially be applied for women at high risk for EOC, and our study promises to contribute to developing a screening protocol for the general population.

1H NMR based profiling of spent culture media cannot predict success of implantation for day 3 human embryos

“…For set 1 of media samples, NMR data were acquired (total measurement time 354 h; Table 2) at 25°C using a Varian Inova 600 spectrometer equipped with a PROTASIS® micro-flow probe connected to an auto-sampler as described previously [29], processed following established standard operating procedures [29], and high spectral quality was validated as described elsewhere [7]. For Sets 2 to 5, NMR samples were prepared by combining 14 μL of media sample with 28 μL of a D 2 O stock solution containing the internal standard formate (1.0 mM) and NaCl (0.9 %w/v).…”

“…1 H Carr-Purcell-Meiboom-Gill (CPMG) spectra was acquired for all sample sets, as we have done before [7]. NOESY spectra [7] acquisition was limited to Set 1, 2 and 3 given that no additional information was gained by this analysis after preliminary review.…”

“…NOESY spectra [7] acquisition was limited to Set 1, 2 and 3 given that no additional information was gained by this analysis after preliminary review. To alleviate the impact of variations of the complex 1 H NMR profile of SSS (Set 5), spectra acquired for control samples were subtracted from the spectra acquired for spent media samples.…”

Metabonomics studies on serum and urine of patients with breast cancer using 1H-NMR spectroscopy

“…Proton nuclear magnetic resonance ( 1 H NMR) spectroscopy is especially sensitive because protons are present in virtually all metabolites [8].…”

Metabolic Profiling of Patients Undergoing Elective Aortic Aneurysm Repair Surgery: Correlation with Anaerobic Threshold

“…NMR spectroscopy has advantages over MS in that it requires minimal sample preparation, is nondestructive to the sample, and produces data with a greater reproducibility. NMR-based metabolomics has been used for biomarker identification in a wide range of fields; recent examples include diagnosis of earlystage epithelial ovarian cancer [25], diagnosis of cerebral infarction [26], identifying severity of chronic liver failure [27], and diagnosis of children with asthma [28]. Of particular significance to the current study is the recent investigation of metabolic changes in traumatic critically ill patients [29].…”