The Study Of Expression Of KLK14 As Well As Its Relationship With Expression Of CA₁₂₅ In Ovarian Epithelial Carcinoma

Ovarian cancer (OC) is one of three kinds of malignant tumor in female genital system, the disease incidence presents raised tendency. Beacause of its particularity of biological quality, it lack early symptom and typicall clinical manifestation, most ovarian cancer patients present with disease of advanced stage so ovarian cancer patients have a poor prognosis and the five year survival stage is only about 25%～30%. Therefore the prognosis of ovarian cancer is closely correlated with detection of early period.CA₁₂₅ widespreadly appear in various kinds of tissues and tumors which originate from colomic epithelium, it is one kind of glucoproteins which exist in cellular membrane of epithelium ovarian cancer. It is considered as epithelial cancer's marker with higher specificity, it is generally used in the diagnosis, differential diagnosis and observation of curative effect in ovarian cancer. Afterwards it was discovered that higher level of CA125 in blood serum didn't occur only in epithelial ovarian tumor, but also oddur in endometriosis, liver cirrhosis and so on. At present, CA125 is still one of the most frequently used tumor biological markers in ovrian tumor, but because it has a low rate in earlier ovrian cancer, when the ovrian cancer patients were final diagnosised, about 40%⁶0% of them already entered advanced stage, so they have a poor prognosis. Therefore searching significant gynecology tumor biological marker of earlier period for ovrian cancer will play an importanrt clinical role in raising ovrian cancer patient's survival rate. These years, many scholars constantly tried to use different index to detect tumor biological marker of earlier and hoped that they can find a tumor biological marker of earlier with better specificity and higher sensitivity.Human kallikrein gene 14 (KLK14) is a recently discovered member of the tissue kallikrein family of secreted serine proteases, which includes hK3/prostate-specific antigen, the best cancer biomarker to date. Given that KLK14 is hormonally regulated, differentially expressed in endocrine-related cancers, and a prognostic marker for breast and ovarian cancer at the mRNA level, we hypothesize that its encoded protein hK14 may constitute a new biomarker for endocrine-related malignancies.These years, there are many tumor markers concerned with diagnosis of ovrian cancer, especially there are a lot of researches about CA₁₂₅, but there are few reports that detected both KLK14 and CA₁₂₅ in ovrian cancer. The objective of this study was to prove that, KLK14 is a tumor maker for ovarian cancer with better sensitivity and higher specificity.ObjectiveBy detecting expression of KLK14 and CA125 in ovrian epithelial cancers and analyzing the relation with its clinical pathological character, we want to reveal the role of KLK14 in the growth and progression of ovrian cancer, supply valued rationale for approaching tumor markers of ovrian cancer.Materials1. Collect paraffin imbedding ovarian tissues of 85 ovarian epithelial tumors and 10 hysteromyoma patients, who have integrity data of pathology and clinic, underwent gynecological operative procedures at the Department of Gynecology, the First Affilated Hospital, Zhengzhou University, from 2004 to 2005. All the patients didn't have any radiotherapy, chemotherapy and other therapy before operation. among the total, there are 65 malignant ovarian tumor (include 45 serous cystadenocarcinoma, 15 mucous cystadenocarcinoma, 5 Endometrioid carcinoma), 10 borderline ovarian tumor (include 6 borderline serous cystadenoma, 4 borderline mucous cystadenoma), 10 benign ovarian tumor (include 8 serous cystadenoma, 4 mucous cystadenoma).2. When the patients didn't have any therapy before operation, draw-off 2 ml venous blood when the patients on an empty stomach, abstract blood serum waiting for measure. At equal pace, collect all the patients' integrity data of pathology and clinic, such as quantity of ascitic fluid, gross tumor volume, information about absorbent gland's metastasis.Methods1. Streptavidin-Peroxidase(S-P) immunohistochemistry technique was used to detect the expression of KLK14 and CA₁₂₅ protein in 85 ovarian epithelial tumors and 10 normal ovarian tissues.2. Bouble antibody sandwich method was used to detect the level of CA₁₂₅ protein in venous blood serum before the ovarian tumors patients have operation .3. Statistical analysis was performed by the SPSS 13.0 software package. Differences among groups were analyzed by using the Chi-squared test, rank-sum test, Kruskal-Wallis test, Independent-Samples T test. Associations between two variables were assessed by the Spearman correlation test. Statistical significant level was considered as"alpha equals 0.05".Results1. According to immunohistochemistry results in 95 ovarian tissues, the positive rate of KLK14 protein expression in normal ovaries, benign ovarian epithelial tumors, borderline ovarian epithelial tumors and ovarian epithelial carcinomas were 10%, 30%, 60%, 95.38% respectively, the positive rate of CA₁₂₅ protein expression in normal ovaries, benign ovarian epithelial tumors, borderline ovarian epithelial tumors and ovarian epithelial carcinomas were 30%, 40%, 70%, 96.92% respectively. The expression of KLK14 and CA₁₂₅ protein in ovarian epithelial carcinomas was significant higher than that in normal ovaries, benign ovarian epithelial tumors and borderline ovarian epithelial tumors (P<0.01).2. The expression of KLK14 and CA₁₂₅ protein in ovarian epithelial carcinomas was significantly associated with the patients' advanced stage of disease, higher tumor grade,more quantity of ascitic fluid, positivity of absorbent gland and histological category (P<0.05); wasn't significantly associated with the patients' elder age, menopause and diameter of gross tumor (P<0.05). The expression of KLK14 and CA₁₂₅ protein in serous cystadenocarcinoma was significant higher than that in mucous cystadenocarcinoma and Endometrioid carcinoma (P<0.01).3. The correlation between the expression of KLK14 and CA₁₂₅ protein in ovarian tissues: The Pearson Correlation between them was 0.605, P=0.000. There was positive correlation between the expression of KLK14 and CA₁₂₅ protein in ovarian tissues. 4. The level of CA₁₂₅ protein in serum: The level of CA₁₂₅ protein in serum of ovarian epithelial carcinoma patients was significant higher than that of benign ovarian epithelial tumor patients (P<0.01). The level of CA₁₂₅ protein in serum of ovarian epithelial carcinoma patients was significantly associated with the patients' advanced stage of disease, higher tumor grade,more quantity of ascitic fluid, positivity of absorbent gland and histological category (P<0.05); wasn't significantly associated with the patients' elder age, menopause and diameter of gross tumor (P>0.05). The level of CA₁₂₅ protein in serum of serous cystadenocarcinoma was significant higher than that of mucous cystadenocarcinoma (P<0.01).5. The correlation between the expression of CA₁₂₅ protein in ovarian tissues and the level of CA₁₂₅ protein in serum: The Pearson Correlation between them was 0.636, P=0.002. There was positive correlation between the expression of CA₁₂₅ protein in ovarian tissues and the level of CA₁₂₅ protein in serum.Conclusions1. KLK14 plays an important role in the malignant transformation, proliferation and advancement of ovarian epithelial carcinomas. There was positive correlation between the expression of K.LK14 and CA₁₂₅ protein in ovarian epithelial tumor tissues. This means that there are synergistic effect between them and they both result in the progression and metastasis of carcinoma.2. The expression of KLK14 and CA₁₂₅ protein in ovarian epithelial carcinomas was significantly associated with the patients' advanced stages of disease, higher tumor grades and positivity of absorbent glands, as the clinical stage, pathological grade and absorbent gland's metastasis are closely correlated with the patients' prognosis of ovarian carcinoma, so detecting both KLK14 and CA₁₂₅ may have prognostic value in epithelial ovarian cancer.3. KLK14 and CA₁₂₅ can be used in the differential diagnosis between serous cystadenocarcinoma and mucous cystadenocarcinoma.