Prognostic Significance Of Acetylated TP53^k382 And SIRT1Expression By Human Ovarian Carcinoma

Background:ovarian cancer （EOC, Epithelial Ovarian Cancer） is oneof the most common gynecological malignancies.2012NCCNrecommend that ovarian cancer chemotherapy preferred with paclitaxel+cisplatin or carboplatin. Apoptosis induced by chemotherapy drugsinclude two paths: death receptor-mediated pathway andmitochondria-mediated pathway, and TP53lead tumor cells to apoptosisthough regulating the activity of mitochondria. Almost all of the cellularstress response are associated with increased level of TP53acetylation,which play an important role inTP53-mediated apoptosis. SIRT1（silentinformation regulator factor1）, which is a subtype of class III of thehistone deacetylase enzymes （HDAC）, can be related to apoptosisthrough the deacetylation the TP53protein at the sit of382lysineresidues, decreased the stability and activity of TP53, avoid apoptosis tobe survived. Recently, several studies reported that SIRT1in multipletumor cell lines and solid tumor tissues showed high expression state,sospeculated that SIRT1is a tumor-promoting agent. However, there is nolarge number of clinical studies in ovarian cancer,whether the expressionlevel of acetylated TP53^k382and SIRT1be in correlation, as well as thepatient prognosis. The purpose of experiment is to detect that is there any coraltion between acetylated TP53^k382and SIRT1expression in ovariancancer patients, and whether the the expression level is associated withthe patient’s survival prognosis, to provide experimental basis anddirection for new clinical treatment strategy.Methods:1.EnVision two-step immunohistochemical methoddetected103cases of ovarian tissue samples, including ovarian cancer65cases of borderline ovarian tumors in12cases,12cases of benign ovariantumors and normal ovarian tissue in14cases;2. Collected65cases ofmalignant ovarian tumors in patients with clinical and pathological data,including age, FIGO stage, Pathology, Histological grade, MalignantCells in ascites or hydrothorax, Liver,lung or Vaginal metastasis,Residual tumor and survival time;3. analysis the expression of acetylatedTP53^k382and SIRT1in four types of ovarian tissue with prognosis inpatients.Results:1. the acetylated TP53^k382and SIRT1was expression in fourtypes of ovarian tissue, but the expression in malignant ovarian tumortissues was significantly higher than normal, benign and borderlineovarian tissue;2. the relationship between acetylated TP53^k382and SIRT1expressionin malignant ovarian tumor is in negative correlation;3. the high expression of acetylated TP53^k382is a positive prognosticfactors, the high expression of SIRT1are adverse prognostic factors in the prognosis of patients with ovarian cancer. Cox proportional hazardsanalysis show that the acetylated TP53^k382is an independent prognosticfactors to DFS and OS in ovarian cancer, the higher the that acetylatedTP53^k382expression, the better the prognosis.Conclusions:1. Acetylated TP53^k382and SIRT1in normal, benign,borderline and malignant ovarian tissue were expressed, but wereoverexpressed in malignant ovarian tumor tissue state.2. In malignant ovarian tumor tissues, the expression of acetylatedTP53^k382and SIRT1is a negative correlation.3. Acetylated TP53^k382is an independent prognostic factors in ovariancancer with DFS and OS.4.In ovarian cancer, the high acetylated TP53^k382in expression is apositive prognostic factors, SIRT1expression is a poor prognostic factor.