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UPLC-LTQ Orbitrap-based Metabonomics Study Of Endometrial Cancer And The Effect Of Body Fat Changes On The Effect Of EC/AH Conservative Treatment

Posted on:2020-07-09Degree:DoctorType:Dissertation
Country:ChinaCandidate:J Q ChenFull Text:PDF
GTID:1364330578483740Subject:Clinical medicine
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BackgroundMetabolomics is a new subject which is widely used in the research of many kinds of tumors.Type 1 endometrial cancer is a hormone-dependent tumor,which is closely related to metabolism.Type 2 endometrial cancer has no relationship with estrogen and poor prognosis.Metabolomics technology can be used to search for molecular targets of endometrial cancer for screening,prognosis and treatment guidance.With the improvement of living standards,the incidence of endometrial cancer continues to increase in young women.Most of these patients are early-stage,highly differentiated endometrial cancer,and most of them are associated with obesity,with a good prognosis.Fertility-sparing therapy give them the opportunity to reproduce.Adipose tissue plays an important role in the development of endometrial cancer,and the effect of body fat changes on conservative treatment of endometrial cancer is still limited.Objectives1.Metabolites between patients with endometrial cancer and the control group and between different types of endometrial cancer were obtained by using the metabolomics technology based on UPLC-LTQ orbitrap,so as to search for potential differential metabolic pathways and search for potential molecular markers for early diagnosis and prognosis.2.To study the effect of body fat changes on the fertility-sparing therapy effect of EC/AH.Methods1?We selected 46 patients.In low-risk group,22 patients were type I endometrial cancer which are moderately or high differentiation and I A period(FIGO 2010).4 patients of type II endometrial cancer and 9 patients of high-risk type I endometrial cancer were selected for high-risk group.11 patients with benign disease were selected for the control group.Plasma and urine samples were collected from three groups of patients.Differential metabolites were screened to find relevant differential metabolic pathways.2?We selected 24 EC/AH patients who received fertility-sparing therapy and satisfied the following conditions:BMI before treatment was over 25kg/m2,and they had not received treatment in other hospitals.Body fat data were obtained by InBody720 body composition analysis prior to treatment and prior to each hysteroscopy.Differences in BMI,body fat and body fat rate were compared between patients with complete remission and those without complete remission at 3 months.Results1?In the urine samples,64,80 and 77 different metabolites were identified between the low-risk group and the control group,the high-risk group and the control group,the high-risk group and the low-risk group,respectively.In the plasma samples,28,27 and 24 different metabolites were identified between low-risk group and control group,high-risk group and control group,high-risk group and low-risk group,respectively.Important metabolic pathways involved include pantothenate and coenzyme A synthesis,purine metabolism,cysteine and methionine metabolism,pyrimidine metabolism,arachidonic acid metabolism,and steroid hormone metabolism.2?Patients with remission after 3 months of treatment showed better fat loss than those without remission,but there was no statistical significance.Conclusions1?Metabolomics differences in plasma and urine of the three groups of patients showed that pantothenate and CoA synthesis,purine metabolism,cysteine and methionine metabolism,pyrimidine metabolism,arachidonic acid metabolism,and steroid hormone metabolism may play an important role in the development of endometrial cancer.2?Fat loss may have a positive effect on conservative treatment-The effect of body fat on EC/AH conservative therapy needs further study.
Keywords/Search Tags:Metabolomics, endometrial cancer, differential metabolites, fertility-sparing therapy for early endometrial cancer/atypical hyperplasia, body fat
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