The Research Of Early Diagnosis And Critical Technology Of Ovarian Cancer

Background:Ovarian cancer is the highest fatality rate in malignant tumors of thegynecologic oncology. Because of no obvious clinical symptoms,60-70%patients are inthe advanced stage in clinic. With surgery, radiotherapy, chemotherapy are improved, the5-year survival rate raise only from37%to46%; it is greater than90%in I stage, so earlydiagnosis is the key to improve patients'5-year survival, but only23%ovarian cancer canbe diagnosed in early stage. Consider the reasons: pathological types of ovarian cancer aremore; the mechanism is not clear; lack tumor markers with high specificity and sensitivity;the occurrence of molecular biology mechanism is not yet perfect. Therefore, there is noideal marker can be applied to clinic to do the early diagnosis in early stage.Objective: Use of serum peptides and two-dimensional electrophoresis method toscreening a new protein/peptide markers, and use HE4immunohistochemical staining inovarian serous adenocarcinoma paraffin tissue, combined with results of clinicalexamination, to explore the relevance both protein/peptide, expression of HE4and theclinical characters of ovarian serous adenocarcinoma.Methods:1. Use MALDI-TOF-MS to analyse the serum peptide map, throughFlexananlysis software to deal the map, then analyzed by use of ClinprotoolsTM2.1software to establish diagnosis model, select the validation group to validate the model.2.Use the two-dimensional electrophoresis to screening the different protein andidentification.3. Using HE4antibody by immunohistochemical methods to do detectionthe primary serous ovarian cancer tissue, to explore the correlation of HE4and clinicalfeatures.Results:1. There are17peptide peaks between ovarian cancer and healthy women, up13, down4, the diagnostic model shows that the sensitivity is100%, specificity is92.0%,and m/z3373,3342,4791,6948can be used as a diagnostic cut-off point. The accurancyof the model is100%.2. There are19peptide peaks between ovarian endometrial cysts and healthy women, up15, down6, the model sensitivity is81.3%, specificity is100.0%,and m/z3342,6689can be used as a diagnostic cut-off point.3. In the model of theovarian cancer and ovarian endometrial cysts, the sensitivity is64.7%, the specificity is75%.4. II stage ovarian serous adenocarcinoma and ovarian endometriotic cysts, screeningout the7protein, two down-regulated, five up-regulated, after mass spectrometry identified,the up-regulated protein are CRBP-2, Nm-23, chaperonin10, Transgelin, down-regulatedproteins are Myl-9, RBP-1, Transgelin-2.5. HE4is high expression in primary ovarianserous carcinoma, there is expression in the tissue of the no TIC oviduct. There is nocorrection of the positive expression rate between the age, pathological grade and themaetastasis of lymph node and HE4expression, but there is relationship between stage andHE4expression.Conclusion:1. Ovarian cancer and healthy women, ovarian endometriosis cyst andhealthy women can be distinguished by the serum peptide diagnostic model, and show thatthe accuracy of the ovarian cancer diagnosis model is higher than serum CA-125. Thismodel can be used to initial diagnosis the ovarian cancer and endometriosis, the malignantbehavior of ovarian endometriosis and ovarian cancer in some certain degree havecorrelation.2. Myl-9, Nm23have related to the development of tumor, Transgelin,Transgelin-2have related to the early metastasis, CRBP2the RBP1may become a targetfor targeted therapy, can be used to further the molecular mechanism.3. HE4maybe play acertain role in the development of primary serous ovarian cancer, and promote to theadvanced cancer, so HE4is expected to be indicators to do early diagnosis, but not entirelytumor metastasis-related factors.