Study On Differences Between Metabolites Of Patients Before And After The Operation Of Hepatocellular Carcinoma

Objectives Metabonomics technology can quantitative determination of endogenous metabolites in nature as a whole and its change rule under the condition of specific environment and time, to determine normal metabolism, and how to put the abnormal metabolic mechanism applied to clinical. The study, through analyzing the hepatocellular carcinoma (HCC) patient before and after surgery serum metabolite profiles tested by the Ultra-performance liquid chromatography combined with mass spectrometry (UPLC-MS), to interpretation the change situation of the small molecule endogenous material from the perspective of the body more intuitive before and after the surgery for liver cancer by contrast healthy crowd. And analysis the trend in the metabolism of information, screening the significant difference characteristic metabolites, then analysis these substances involved in metabolic pathways and the value to diagnosis of liver cancer, in order to be conducive a more comprehensive understanding of the cancer of the liver disease, opening up new horizons for clinical diagnosis and treatment.Methods The serum before and after operation were sampled from15patients hepatitis B virus related HCC, who were admitted radical resection in the liver surgery department of Tianjin Third Central Hospital from Mar,2011to Jun,2012. The preoperative serum for admission standards were at the beginning of fasting morning serum samples without any treatment, and the postoperative serum for the patients with radical surgery in7days fasting morning serum specimens. All patients are the stages of Al liver cancer Stage according to the Barcelona clinical stages.8cases of men and7cases of women. The specimens were tested by a UPLS-MS platform after a pretreatment procedure. The raw data were firstly processed by MZmine2.0software before being analyzed by SIMCA-P+12.0.1.0(Sweden Umetrics Company). Orthogonal partial least squares discriminate analysis (OPLS-DA) model were constructed from the tissue metabolite profile data, variable importance in projection (VIP) and VIP confidence of which were then used to select potential biomarkers. Non-parametric test by SPSS17.0(SPSS, USA) were used to exclude variables with p>0.05from these selected potential metabolite biomarkers, and analyzed the trend of differences metabolites change and discussed its clinical value.Results (1) The OPLS-DA models based on the serum metabolite profiles before and after surgery in HCC patients is good enough to separate normal tissue, transitional tissue and tumor tissue.(2)27metabolite ions were discovered to play important roles in separating different tissues, of which8metabolites tend to normal with the resection of the tumor in the serum levels, shows cancer tissue are the important factors that affect these characteristics metabolites change, and of which36metabolites were identifications. They are LysoPC(16:0), Estradiol, Glycoursode-oxycholic acid, Alpha-Tocotrienol, PA(16:0e/18:0), Oleoylcarnitine, L-Palmitoylcarnitine. Statistical analysis and ROC curves showed that the characteristics of metabolites with high correlation in patients with carcinoma in or out the body, and has potential clinical value on the thorough analysis and research.Conclusions This study indicate that7high characteristic metabolites have special change in the relevance of liver cancer, LysoPC (16:0), Estradiol, Glycoursodeoxy-cholic acid, Alpha-Tocotrienol, PA(16:0e/18:0), Oleoylcarnitine, L-Palmitoylcarnitine of liver cancer research on hepatitis B related metabolic profile before and after surgery with radical resection. these metabolites has potential application value in diagnosis, prognosis and relapse for liver cancer. it helps to understand the molecular mechanisms of the disease and provide a new direction for clinical diagnosis and treatment by the study of endogenous metabolites and metabolic pathway.