| Ovarian cancer has the highest mortality of all gynecological malignancies. Because the symptoms of early-stage ovarian cancer are not specific, it is not easy to detect. In the majority of patients, ovarian cancer is not detected until late stages. It is particularly important to improve the early diagnostic rate of ovarian cancer. Transforming growth factor-β(TGF-β)plays a negative role in normal cells growth regulation, it plays its biological effects in a broad range, not only the regulation of cell proliferation, differentiation, migration and apoptosis, but also the close relationship with extra cellular matrix production, the immune suppression and opportunistic infections. TGF-β1 is the main form of TGF-βand it is the most active.Smad4 is a central component of the TGF-βsuperfamily signaling pathway. The mutations and deletions of Smad4 are seen in about 50% of pancreatic cancers.TGF-β1 and Smad4 play important roles in human tumorigenesis. This experiment aims to detect the levels of TGF-β1 and Smad4 in serum and Smad4 expressive profiles in patients with ovarian tumors and normal ovaries in order to provide some experimental reference for the pathogenesis, diagnosis, monitoring, treatment, and prognosis of ovarian cancer.Materials and Methods: Enzyme-Linked Immunosorbent Assays is used to detect the serum levels of TGF-β1,Smad4 and Immunohistochemistry is used to detect Smad4 expressive profiles in patients/women with ovarian cancer, borderline ovarian tumor, benign epithelial ovarian tumor ,ovarian sex cord-stromal tumor and the normal ovaries.Results:1,The preoperative serum levels of TGF-β1 in patients with ovarian cancer show no statistical difference with borderline ovarian tumor and ovarian sex cord- stromal tumor(P>0.05),but they are all significantly higher than the serum levels of TGF-β1 in patients with benign epithelial ovarian tumor and the normal ovaries, which are statistically significant difference(P<0.01). The preoperative serum levels of TGF-β1 in patients with benign epithelial ovarian tumor are significantly higher than the normal ovaries, which are statistically significant difference (P<0.01). After operations, the serum levels of TGF-β1 in patients with ovarian cancer, borderline ovarian tumor, benign epithelial ovarian tumor ,ovarian sex cord-stromal tumor and the normal ovaries are all significantly higher than the preoperative serum levels, which are statistical difference (P<0.05) ,but they all show no difference(P>0.05). The preoperative serum levels of TGF-β1 in patients with ovarian cancer are related to histological type and the volume of ascites , which are statistical difference (P<0.05).2,The preoperative serum levels of Smad4 in patients with ovarian cancer, borderline ovarian tumor, benign epithelial ovarian tumor and ovarian sex cord- stromal tumor are higher than the serum levels of Smad4 in patients with the normal ovaries , which are statistical difference (P<0.05). After operation , the serum levels of Smad4 in patients with ovarian cancer are lower than the serum levels of Smad4 in patients with benign epithelial ovarian tumor and ovarian sex cord- stromal tumor, ,which are statistical difference (P<0.05). The postoperative serum levels of TGF-β1 in patients with benign epithelial ovarian tumor and the normal ovaries are all higher than the preoperative serum levels, which are statistical difference (P<0.05). The preoperative serum levels of Smad4 in patients with ovarian cancer are related to histological grade, histological type and the volume of ascites (P<0.05).3,The expression of Smad4 protein in ovarian epithelial tissues is lost in 38 ovarian cancer tissues(38/82,46.3%) , in 8 borderline ovarian tumor tissues (8/20, 40.0 %),in 14 benign epithelial ovarian tumor tissues(14/24,58.3%),in 4 ovarian sex cord– stromal tumor tissues(4/16,25.0%), and in 2 normal ovaries tissues(2/16,12.5%). Of 82 ovarian cancer specimens,14 are ovarian mucous adenocarcinomas and the expression of Smad4 protein is lost in 12 ovarian epithelial tissues (85.7%); Of 20 borderline ovarian tumor specimens,12 are mucinous ovarian tumors and the expression of Smad4 protein is lost in 6 ovarian epithelial tissues (50.0%); Of 24 benign epithelial ovarian tumor specimens,14 are mucinous cystadenoma of ovary and the expression of Smad4 protein is lost in 10 ovarian epithelial tissues (71.4%).There are benign, borderline and malignant lesions simultaneously in two cases of mucinous ovarian tumors and Smad4 protein is of deficiency expression in above-mentioned lesions. The expression of Smad4 protein is absent in the epithelial tissue of ovarian cancer is higher than the normal ovaries ,which is statistical difference (P<0.05).The expression of Smad4 protein is absent in the epithelial tissue of benign epithelial ovarian tumor is higher than ovarian sex cord-stromal tumor and the normal ovaries ,which is statistical difference (P<0.05).In 82 cases of ovarian cancer, the expression of Smad4 protein is lost in 20 ovarian interstitial tissues (24.4%), but the expression of Smad4 protein in ovarian interstitial tissues is lost in no borderline ovarian tumor tissues, benign epithelial ovarian tumor tissues, ovarian sex cord-stromal tumor tissues and the normal ovaries tissues. In ovarian cancer ,loss of Smad4 protein expression in the epithelial tissues is related to age, histological type, clinical stage, the volume of ascites and pelvic lymph node metastasis (P<0.05). In ovarian cancer ,loss of Smad4 protein expression in the interstitial tissue is not related to all of the clinicopathological factors that we mentioned in this paper(P>0.05).Conclusions: 1,The elevated serum levels of TGF-β1 and Smad4 in patients with ovarian cancer and ovarian sex cord-stromal tumor can be used as the biological indicators for the diagnosis. 2,The elevated serum levels of TGF-β1 and Smad4 in patients with ovarian cancer can be used as the poor prognostic indicator.3,The serum levels of Smad4 may come from the ovarian epithelial tissue and interstitial tissue in patients with ovarian cancer and ovarian sex cord- stromal tumor.4,The loss of Smad4 protein expression in ovarian cancer may be one of the important reasons for the obstacle of TGF-β1-Smad4 signal transduction and may be considered as one of the poor prognostic indicators for some patients.5,The expression of Smad4 protein can not be used as the biological indicator for the differential diagnosis of primary and metastatic ovarian mucous adenocarcinomas.6,The loss of Smad4 protein expression in ovarian cancer indicates that Smad4 may has potentially biological therapy value for some patients.
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