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The Expression And Clinical Significance Of The Human Kallikrein Gene 14 (klk14) In Epithelial Ovarian Cancer

Posted on:2008-05-11Degree:MasterType:Thesis
Country:ChinaCandidate:Z S SongFull Text:PDF
GTID:2144360215960451Subject:Obstetrics and gynecology
Abstract/Summary:PDF Full Text Request
Epithelial ovarian cancer(oc) is the one of the three magligant carcinoma in gynecology,and it also is the leading cause of death from gynecologic cancer.The incidence of the OC is higher and higher.Because of a lack of early warning signs and vague symptomatology, most ovarian carcinoma patients present with widespread metastatic disease . at present,there is no effective screening tool for the general population and the biological mechainism of ovarian cancer is unclear. so, there is no effective way to cure OC and the 5-year survical rate for patients with OC is still around 30%. Thus there is a critical need for a better understanding of the biology of the disease to find the better biological markers and therapies for ovarian carcinoma.Kallikreins are one family of genome.It expressed a lot of tissues.especaily in the cancer tissues They belong to the Serine proteases.Serine proteases comprise a family of protein-degrading enzymes that serve a host of biological functions,including activation of blood coagulation cascades, activation of growth and angiogenic factors, and degradation of extracellular matrix components. In recent years, aberrant expression of serine proteases such as plasminogen activator has been shown to correlate positively with the invasiveness and metastatic potential of tumor cells. Presumably, this occurs because the ability of the tumors to degrade extracellular matrix components is increased, either directly or indirectly through the proteolytic activation of other zymogenic proteases. More significantly, the serine protease known as PSA has been used successfully as a tumor marker for the early diagnosis of prostate cancer due to its abnormal prevalence in the peripheral blood of these patients . Serine proteases play important roles in the cascade of events involved in the malignant process,for the cancer.Human kallikrein gene 14 (klk14) is a recently discovered member of the tissue kallikrein family of secreted serine proteases, klk14 is expressed in many cancers, especially the humon- regard tissue, including breast , prostate, testis and ovarian cancer. klk14 known as serine proteases supports many biological functions for cancer cells, including activation of growth and angiogenic factors and activation of other proteases for invasion and metastasis. In addition, many of these serine proteases are secreted by cells into the extracellular space to serve these functions. Therefore, the klk14 is an excellent candidate tumor markers. The research of it may provide us the new way to understand the mechanism of ovarian cancer and find new method for diagnosis and treatment of ovarian cancer.We study of the expression of klk14 protein in 14 normal ovaries ,28 patient with benign epithelial cancer, 15 patient with borderline epithelial cancer and 70 patients with ovarian carcinoma, and their correlation to clinicopathological features. In addition by using reverse translation PCR ,we detected the mRNA expression of klk14 in 28 patients with ovarian cancers and 10 normal ovaries.ObjectiveTo analyze the role of klk14 in progression and metastasis of the epithelial ovarian cancer by detecting the expression of klk14 protein and its mRNA in ovarian cancer to study the role of the klk14 in the growth and progression of ovarian cancer and future to interpret the possible molecular mechanisms and supply valued diagnosis and prognosis indicators for clinical workers and a new method for gene therapy.Method1. Immunohistochemisty was used to detect the protein expression of klk14 in paraffin specimens from 70 patients with ovarian carcinoma, 15 patients with borderline epithelial cancer, 28 patients with benign epithelial cancer and 14 normal ovaries and the relationships between protein expressions and clinicopathological feature were analyzed accordingly. 2. Revers-tanscription PCR was used to detect the protein expression of klkl4 in 28 patients with ovarian carcinoma and 10 normal ovaries, and the mRNA expression difference between these two tissue and if mRNA levels of these tissues correspond to their protein levels were analyzed accordingly.3. Statistical analysis: the spss statistical package program 13.0 for all analysis. Association between the variables were tested by Chi-square Test , Wilcoxon signed rank test, t test and Fisher exact probability, the Log-Rank analysis,Cox ratio-risk model,Kaplan-model survival curve were use in the analysis of the prognosis.Result1. The relative expression level of klk14 mRNA in normal ovary and ovarian carcinoma is 0.63±0.19 and 1.36±0.24 respectively.The relative expression of the OC is higher than in the normal ovary. There is the statistical difference(t=-8.432,P<0.01) .2. According to immunochemistry results in ovarian tissue, the positive rate of klk14 protein expression in normal ovarian , benign ovarian rumors, borderline ovarian tumors and ovarian carcinoma were 14.3% (2/14), 17.9% (5/28), 53.3%(8/15) , 61.4% (43/70) respectively. There were significant differences (X~2 =21.648, P<0.01). Namely, along with the increase of the malignancy degree of ovarian carcinomas, the positive rates of klk14 increased.3. The protein level of klk14 overexpression in epithelial ovarian cancer was significantly associated with advantaged stage of disease,higher tumor grade and positivity of nodal.4. The expression of klk14 and the patients' prognosis are inverse correlation. multiple factor Cox recur analysis display that the expression of klkl4 is the independent risk factor for the prognosis of the OC.Conclusion1. The expression of the protein klk14 and its mRNA are corresponding with the malignant level of the OC. It may play some role in the origination and progression of ovarian cancer.2. The expression level of the protein klk14 was correlated with clinical stage, pathological grade. It interprets that the klk14 protein maybe a novel biological marker for monitoring the ovarian cancer in clinic.3. The expression of protein klk14 and the patients' prognosis are correlation and the expression of the protein klk14 may have prognosis value in epithelial ovarian carcinoma.
Keywords/Search Tags:klk14, epithelial ovarian carcinoma, Immunohistochemisty, RT-PCR, prognosis
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