Expression Of HIF-1α And STAT3 In Ovarian Serous Carcinoma And Its Clinical Significance

Ovarian cancer is one of malignant tumors of female reproductive system. Ovarian serous adenocarcinoma is the most common malignant epithelial tumor of ovary, with progress fast, easy to recurrence and metastasis and drug resistance, not easy to be found early, therefore, searching for biomarkers of tumor specific, for the early detection of ovarian serous carcinoma and molecular targeted therapy provides theoretical basis for this study was imminent.Hypoxia inducible factor-1 alpha(HIF-1α) is a kind of nuclear transcription factor under hypoxic conditions which are widely expressed in mammalian and human. It is the core of control status in cell hypoxia signaling pathways. HIF-1αcan make tumor adapt to hypoxia microenvironment by enhanced cell viability in hypoxia environment and promote malignant transformation of angiogenesis. Hypoxia-inducible factor 1(HIF-1) is a potent tumorigenic factor. Its alpha subunit, which is tightly regulated in normal tissues, is elevated in tumors due to hypoxia and overactive growth signaling pathways. In addition, HIF-1αcan also induce tumor cells to radiotherapy and chemotherapy tolerance and promote tumor proliferation, invasion and metastasis etc.. Additionally, whether and how the tumor microenvironment contributes to HIF-1αaccumulation is unclear. Further study still await.In recent years, the role of Stats signaling pathway in the occurrence of cancer is gradually taken by the people. STAT3 signal transducer and activator of transcription 3(STAT3) is a key signaling pathways of Stats signaling pathway in the family. It is defined as a cancer gene and showed high expression of the state in a variety of tumors. The activation of STAT3 protein in normal signal transduction is fast and transient. Its sustained activation of STAT3 cell malignant transformation process and is closely related to abnormal cell proliferation and malignant transformation abnormal cell. STAT3 is involved in tumor occurrence and development through promote the proliferation of tumor cells, inhibit tumor cell apoptosis, angiogenesis, tumor invasion and metastasis, etc. to promote the mechanisms.At present, the domestic and foreign research shows a variety of cancers(breast cancer, gastric cancer, liver cancer, pancreatic cancer, prostate cancer, endometrial cancer) expression of HIF-1αand STAT3 activity were increased. HIF-1αand STAT3 was detected by immunohistochemical method in ovarian serous adenocarcinoma of expression, rarely at home and abroad the report. Therefore, this experiment using immunohistochemical method to explore the relationship between expression of HIF-1αand STAT3 in ovarian serous carcinoma. And whether the expression intensity classification is associated with the grading of ovarian serous carcinoma. It has important clinical significance on early discovery, early treatment and judging prognosis in ovarian cancer.Objective: To explore the HIF-1α, STAT3 in ovarian serous carcinoma occurrence, its mechanism may exist by detecting the expression of both HIF-1α and STAT3 in ovarian serous carcinoma and clinicopathological relationship, and provides guidance significance for ovarian cancer molecular targeted therapy.Methods:1 80 cases of ovarian serous adenocarcinoma specimens and 20 cases of normal ovary tissues were collected from the fourth hospital of Hebei Medical University during 2009 December to 2014 December. And retrospective study of clinical and pathological data of the corresponding, and follow-up observation of ovarian serous adenocarcinoma prognosis and survival condition.2 To detect the expression of HIF-1α, STAT3 in 80 cases of ovarian serous carcinoma and its correlation with clinical pathology by using immunohistochemistry respectively, and 20 cases of normal ovary tissues as control. HIF-1α, STAT3 in ovarian cancer and its possible mechanisms was analogized.Results:1 In normal ovarian tissue, low grade and high grade ovarian serous carcinoma, statistic significance were found in each groups. The positive rate of HIF-1α were 5%, 83.33%, 63.51%; the positive rates of STAT3 were 15%, 66.67%, 75.68%(P<0.05).2 In ovarian serous adenocarcinoma tissue, in 50 years old age group and the >50 age group, clinical stage I ~ II and III ~ IV group, lymph node metastasis group, the positive rate of HIF-1α were 34.48% and 82.35%(P<0.05), 41.18% and 82.61%(P<0.05), 68.42% and 15.38%(P<0.05), statistic significance were found in each groups; STAT3 were 75.86% and 78.43%(P>0.05), 75.86% and 78.43%(P>0.05), no significant differences were found in this group, 61.76%和 89.13%(P<0.05), 63.16% and 23.08%(P<0.05), 34.48% and 82.35%(P<0.05), statistic significance were found in each groups. The staining intensity of HIF-1α and STAT3 were associated with low and high grade serous ovarian adenocarcinoma by Spearman rank correlation analysis(r>0, P>0.05), but no significant differences were found in each groups.3 Using Kaplan-Meier method through single factor analysis of survival, the survival rate was compared with the Log-rank test. The survival rates of HIF-1α and STAT3 positive group were lower than negative group survival rate(P<0.05). Statistic significance were found in each groups.Conclusions:1 HIF-1α and STAT3 was significantly over expression in ovarian serous adenocarcinoma may be involved in the process, the occurrence, development of tumor.2 HIF-1α and STAT3 in ovarian serous carcinoma is involved in tumor invasion and metastasis. It may become one of the adverse factors to assent the progress of ovarian serous adenocarcinoma.3 HIF-1α and STAT3 positive is a bad influence factors of ovarian serous cancer which impact on the survival rates.