Font Size: a A A

The Expression And Clinical Significance Of TUBB3、ERCC1and P-gp Protein In Ovarian Cancer

Posted on:2015-04-10Degree:MasterType:Thesis
Country:ChinaCandidate:J ZhangFull Text:PDF
GTID:2284330431980608Subject:Oncology
Abstract/Summary:PDF Full Text Request
Ovarian cancer (OC) is one of the common malignant tumor ofdepartment of gynaecology, the incidence of ovarian cancer in our countryhas a rising trend in gynecological tumors of the second[1], at the same timethe age tend to be younger.The onset of hidden,most diagnosed when alreadybelongs to late,although5years of survival rate increased,up to now stillamounted to less than50%.Ovarian cancer is one of the major diseaseserious threat to women’s health.At present, the treatment of ovarian cancerwith surgery, chemotherapy and radiotherapy, but chemotherapy in thetreatment of ovarian cancer occupies in the process of an important position.The multi-drug resistance of tumor cells to chemotherapeutic drugs(multidrug resistance, MDR) is one of main chemotherapy failed reasons andled to one of the main causes of death in patients with tumor recurrence,progression, and the leading cause of death.By a variety of genes, morefactors and complex multi-step process to produce tumor drug resistance,P-glycoprotein(P-gp) which coded by drug-resistant genes MDR1highexpression was one of the main reasons that generated multidrug resistance(MDR), it was the only confirmed in clinical practice, overcome this obstacle,chemotherapy will gain a decisive breakthrough. Ovarian cancer treatment isyew class joint platinum of standard chemotherapy, some patients is notsensitive to yew and platinum drugs, the effect is bad, if the patients withgood sensitivity to yew and platinum drugs of ovarian cancer, it can beimprove efficient and prolong patient survival benefit ofchemotherapy.Therefore explore predictors of platinum and yewchemotherapy sensitivity is very important to guide clinical rational drug use.TUBB3gene (class III beta-tubulin, beta tubulin III) is an importantcomponent of the cytoskeleton, exists in all eukaryotic cells and someprokaryotes, maintain cell morphological structure and participating in sports,in cell growth, division, apoptosis and plays an important role in informationtransmission, and yew drugs can specificity combined with beta tubulin III,through the combined with microtubules and block the depolymerization,prevent the completion of mitosis, inducing cell apoptosis, and thus play arole of anti-tumor.Studies have shown that TUBB3and yew, such asresistance to microtubules is closely related to the chemotherapy drugresistance, its high expression can reduce yew drugs of tubulindepolymerization, resulting in its resistance.Nucleotide excision repair cross complementary gene1(excision repaircross complementing group1, ERCC1) have the function of theidentification of DNA damage and chain between the cutting, nucleotidesshear repair process is one of the key enzyme, the expression can make thestagnation of tumor cells in G2/M phase, the DNA damage repair quickly,causes the resistance of platinum drugs.P-glycoprotein (P-glycoprotein, P-gp) is ATP dependent transmembraneprotein, not only may amount dependence to drug pump out of cells, preventdrug transport into the cell, reduce the accumulation of intracellulardrug;also for intracellular drug distribution changes, some drugs are gatheredin organelles does not produce its own role, make the drug to reach curativeeffect, which can lead to drug resistance.Objective:To investigate the expression of TUBB3, ERCC1and P-gp protein inovarian cancer tissue and normal ovarian tissue, analyze these respectivelythe relationship between the clinical pathologic factors associated withovarian cancer;TUBB3, ERCC1and P-gp expression in ovariancancer,predicting ovarian cancer patients on the drug sensitivity and provideevidence for individualized treatment plan. Methods:Collection of surgery and the postoperative pathological diagnosis of50cases of ovarian cancer tissue and normal ovarian tissue (double attachmentno pathological conditions of patients with uterine fibroids surgical removalof the ovaries as normal control group) and25cases of pathological waxblock, will filter out complete clinical data of50patients with ovarian cancer,has not been preoperative chemotherapy, radiation therapy, biologicalimmune therapy.With immune histochemical methods Envision two-stepdetection TUBB3, ERCC1, P-gp expression in ovarian cancer tissue, analysiswith the patients’ age, histology, pathologic stage, the relationship betweenthe clinical stage, tumor location;Application of SPSS17.0statisticalsoftware processing data, categorical data by chi-square test, USESSpearman correlation analysis, correlation with α=0.05as the inspectionstandard, P <0.05for the difference was statistically significant.Results:1.TUBB3and ERCC1, P-gp in expression in ovarian cancer tissue andnormal ovarian tissue, TUBB3positive expression in cytoplasm, in ovariancancer tissue expression positive rate was52.0%(26/50), significantly higherthan that in normal ovarian tissue positive expression was24.0%(6/25),difference was statistically significant (chi-square=7.038, P=0.021).ERCC1positive expression in the nucleus, in ovarian cancer tissue expressionpositive rate was70.0%(35/50), significantly higher than that in normalovarian tissue positive expression was32.0%(8/25), difference wasstatistically significant (chi-square=9.420, P=0.002).P-gp positioning inthe cytoplasm or in the cell membrane, in ovarian cancer tissue expressionpositive rate was85.0%(42/50), significantly higher than that in normalovarian tissue positive expression was40.0%(10/25), difference wasstatistically significant (chi-square=15.176, P=0.000).2.Ovarian cancer at the protein level in the organization TUBB3, theexpression of ERCC1and P-gp associated with pathologic grading andclinical staging (all P <0.05), including tumor stage all the expression level of higher and higher, and in terms of pathologic stage, is also the tumordifferentiation degree low expression level higher and higher, but the threewith the patient age, histological type, location had no statistical difference(P>0.05).3. The positive expression rate of ERCC1in ovarian cancer tissue washigher than the expression of P-gp, there was no statistically significantdifference between (P>0.05), the expression of ERCC1expression and P-gp has no obvious correlation;While TUBB3expression in ovarian cancertissue was lower than that in group P-gp expression (P <0.05), TUBB3expression and the expression of P-gp negatively correlated (P <0.05);TUBB3expression group is lower than the ERCC1expression inovarian cancer organizations, TUBB3expression and the expression ofERCC1positively correlated (P <0.05).Conclusion:The positive expression rate of TUBB3, ERCC1and P-gp in theovarian cancer tissues was significantly higher than that of normal ovariantissue, is the sensitive index in ovarian cancer detection, and the threeexpression in ovarian cancer tissues were related to tumor pathologic gradeand clinical stage, pathological classification, the lower the longer the higherthe positive rate of expression and the clinical stages, prompt the three withthe occurrence and development of ovarian cancer and tumor drug resistance;ERCC1and P-gp expression has no statistical significance in ovarian cancertissue, and TUBB3and ERCC1expression in ovarian cancer tissue werepositively correlated, and TUBB3and P-gp expression in ovarian cancerorganizations negatively correlated.Because of the complexity of thechemotherapy drug resistance mechanism, prompt detection at the same timethe three possible as individual chemotherapy for ovarian cancer, one of theimportant indices for detecting sensitivity to chemotherapy and prognosis.
Keywords/Search Tags:ovarian cancer, resistance of microtubules, DNA repair, ATP transporter combination cartridge, TUBB3, ERCC1, P-gp, drugresistance, the prognosis
PDF Full Text Request
Related items