Plasma Metabolic Component Research Of Cervical Carcinoma And Precancerous Lesions In Uyghur Women

Objective:To investigate the metabonomic changes in plasma of Xinjiang Uygurwomen with cervical cancer (Cervical Squamous Cell Carcinoma CSCC), cervicalintraepithelial neoplasia (Cervical Intraepithelial Neoplasia CIN) and healthy controlgroup, the Nuclear Magnetic Resonance (NMR) and High-performance liquidchromatography (HPLC) method based on metabonomics was performed to analyzethe diagnostic feasibility of cervical cancer. For the early diagnosis and early warningsystem of cervical cancer provide some of the theoretical and experimental basis.Method: Plasma samples were taken from114Uighur patients with CSCC (38), CIN(38) and healthy controls (38).1H-NMR based on metabonomics has been used tocharacterize the metabolic profiles of CSCC and CIN. HPLC quantitative detectionwas carried out to determine the differences in metabolic component. Principalcomponent analysis (PCA) and orthogonal partial least-squares discriminant analysis(OPLS-DA) were used to model the systematic variation related to patients with CINor CSCC with healthy controls. One-way analysis of variance (ANOVA) test andT-test were used to examine the significance of the metabolites and identification of avariety of amino acids in plasma samples. Results:1H-NMR results showed that，compared with the plasma of the healthy controls, Plasma from patients with CSCChad higher levels of acetate and formate, together with lower levels of creatine, lactate,isoleucine, etc. Compared with plasma obtained from the healthy controls, plasmafrom patients with CIN had higher levels of very-low density lipoprotein (VLDL),acetone, unsaturated lipid and carnitine, together with lower levels of creatine, lactate,isoleucine, etc. In addition, compared with the plasma of patients with CIN, theplasma of CSCC patients had higher levels of acetate, formate, tyrosine, myo-inositol,etc.Together with lower levels of acetone, unsaturated lipid and carnitine.Moreover,the profiles showed high feasibility and specificity by statistical analysis withOPLS-DA compared to the Thinprep cytology test (TCT) by setting thehistopathological outcome as standard.The metabolic profile obtained for cervical cancer is significant, even for the precancerous disease. This suggests a systemicmetabolic response to cancer, which may be used to identify potential early diagnosticbiomarkers of the cancer and to establish clinical diagnostic methods. The HPLCresults showed that, compared with the plasma of the healthy controls, in plasma ofCSCC a wide range of amino acids including glutamate, glycine, lysine,etc, see asignificant decrease (P <0.05). Compared with the plasma of the healthy controls, inplasma of CIN a wide range of amino acids including glutamate, glycine, threonine,etc. see a significant decrease (P <0.05). Compared with the plasma of patients withCSCC, in plasma of CIN aspartic acid, arginine, phenylalanine see a significantdecrease (P <0.05). No significant differences of glycine, threonine, methionine, etc.were found between CSCCand CIN. Conclusion: There are significant differences ofmetabolic components between plasma of healthy control group, CSCC and CIN. Theprofiles showed high feasibility and specificity compared to the TCT. There aresignificant differences of amino acids between plasma of healthy control group,CSCC and CIN. The decreases of amino acid in plasma of CSCC and CIN can be asspecific potential bio markers of cervical cancer.