Evren C. Eroglu

Discovery of metabolomic biomarkers for discriminating platinum-sensitive and platinum-resistant ovarian cancer by using GC-MS

This study aims to determine ovarian cancer (OC) patients with platinum resistance for alternative treatment protocols by using metabolomic methodologies. Urine and serum samples of platinum-resistant and platinum-sensitive OC were analyzed using GC-MS. After data processing of GC-MS raw data, multivariate analyses were performed to interpret complex data for biologically meaningful information and to identify the biomarkers that cause differences between two groups. The biomarkers were verified after univariate, multivariate, and ROC analysis. Finally, metabolomic pathways related to group separations were specified. The results of biomarker analysis showed that 3,4-dihydroxyphenylacetic acid, 4-hydroxybutyric acid, L-threonine, D- mannose, and sorbitol metabolites were potential biomarkers in urine samples. In serum samples, L-arginine, linoleic acid, L-glutamine, and hypoxanthine were identified as important biomarkers. R2Y, Q2, AUC, sensitivity and specificity values of platinum-resistant and sensitive OC patients’ urine and serum samples were 0.85, 0.545, 0.844, 91.30%, 81.08 and 0.570, 0.206, 0.743, 77.78%, 74.28%, respectively. In metabolic pathway analysis of urine samples, tyrosine metabolism and fructose and mannose metabolism were found to be statistically significant (p < 0.05) for the discrimination of the two groups. While 3,4-dihydroxyphenylacetic acid, L-tyrosine, and fumaric acid metabolites were effective in tyrosine metabolism. D-sorbitol and D-mannose metabolites were significantly important in fructose and mannose metabolism. However, seven metabolomic pathways were significant (p < 0.05) in serum samples. In terms of p-value, L-glutamine in the nitrogen metabolic pathway from the first three pathways; L-glutamine and pyroglutamic acid metabolites in D-glutamine and D-glutamate metabolism. In the arginine and proline metabolic pathway, L-arginine, L-proline, and L-ornithine metabolites differed significantly between the two groups.

GC-MS based metabolite fingerprinting of serous ovarian carcinoma and benign ovarian tumor

The aim of this study is to identify urinary metabolomic profile of benign and malign ovarian tumors patients. Samples were analyzed using gas chromatography-mass spectrometry (GC-MS) and metabolomic tools to define biomarkers that cause differentiation between groups. 7 metabolites were found to be different in patients with ovarian cancer (OC) and benign tumors (BT). R2Y and Q2 values were found to be 0.670 and 0.459, respectively. L-tyrosine, glycine, stearic acid, turanose and L-threonine metabolites were defined as prominent biomarkers. The sensitivity of the model was calculated as 90.72% and the specificity as 82.09%. In the pathway analysis, glutathione metabolism, aminoacyl-tRNA biosynthesis, glycine serine and threonine metabolic pathway, primary bile acid biosynthesis pathways were found to be important. According to the t-test, 29 metabolites were found to be significant in urine samples of OC patients and healthy controls (HC). R2Y and Q2 values were found to be 0.8170 and 0.749, respectively. These results showed that the model has high compatibility and predictive power. Benzoic acid, L-threonine, L-pyroglutamic acid, creatinine and 3,4-dihydroxyphenylacetic acid metabolites were determined as prominent biomarkers. The sensitivity of the model was calculated as 93.81% and the specificity as 98.59%. Glycine serine and threonine metabolic pathway, glutathione metabolism and aminoacyl-tRNA biosynthesis pathways were determined important in OC patients and HC. The R2Y, Q2, sensitivity and specificity values in the urine samples of BT patients and HC were found to be 0.869, 0.794, 91.75, 97.01% and 97.18%, respectively. L-threonine, L-pyroglutamic acid, benzoic acid, creatinine and pentadecanol metabolites were determined as prominent biomarkers. Valine, leucine and isoleucine biosynthesis and aminoacyl-tRNA biosynthesis were significant. In this study, thanks to the untargeted metabolomic approach and chemometric methods, every group was differentiated from the others and prominent biomarkers were determined.