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

Abstract

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.

Keywords: GC-MS; OPLS-DA; benign tumor; biomarker; healthy control; metabolomics; ovarian cancer.