The Expression Of YKL-40 In Tumor Tissues And The Diagnosis Values Of YKL-40,HE4,CA125 Assay In Serum Of Patients With Epithelial Ovarian Cancer

Objective: Ovarian carcinoma is a malignant tumor, which account for most deaths in gynaecological tumour diseases,and its incidence shows an upgrade tendency. Its pathogenesis is hidden, but developed rapidly, about 70~80%of ovarian carcinoma has been in an advanced stage when they were diagnosed, the 5-year survival is about 20%~30%, the main cause is that the patients with early ovarian carcinoma have no symptoms, and no effective early detection techniques have been identified, so how to diagnose ovarian carcinoma early is becoming the urgent problem, which is to be solved. The present researches of ovarian cancer biomarkers focus on YKL-40 and Human Epididymis Protein 4(HE4), while the perfect biomarker should be provided better sensitivity and specificity. This study is to explore the possibility of YKL-40 and HE4 as tumor markers, and compared with CA125, to evaluate their value for early diagnosis, reflecting prognosis, monitoring recurrence. Try to establish a simple, fast, sensitive and specific method.Methods: 1 Immunohistochemistry was used to detect the expression of YKL-40 protein in tissues, among this series, 11 cases were normal ovarian, 20 cases were benign ovarian tumor, 10 cases were borderline ovarian tumor and 30 cases were ovarian carcinoma. The positive cell of staining section was measured by computer image processing software. The positive expression rates of YKL-40 protein in four groups were compared, relationships between the expression of YKL-40 protein and different clinicopathological character in epithelial ovarian cancer tissue were analyzed.2 The double antibody sandwich Enzyme-linked Immu- nosorbent Assay (ELISA) technique was applied to detect serum YKL-40 protein and HE4 protein concentration, among this series, 11 cases healthy women, 20 cases benign ovarian tumor, 7 cases borderline ovarian tumor, preoperative and post- operative ovarian carcinoma each 25 cases, CA125 concen- tration from our laboratory was detected by an electrogenerated chemilumin cence method. The levels of YKL-40,HE4 in each group were compared respectively. The correlations between serum concentration and different clinicopathological character in epithelial ovarian cancer tissue were analyzed.3 when ovarian malignancy was compared with controls having healthy women, benign tumor, healthy women and benign tumor groups respectively. The diagnosis efficiency of the YKL-40 assay and HE4 assay was compared, and the best diagnosis points of the YKL-40 assay and HE4 assay were determined.4 The sensitivity of serum YKL-40,HE4,CA125 whether alone or combined in diagnosing ovarian carcinoma was com- pared. The diagnosis efficiency of the HE4 assay was com- pared, when sets different diagnosis points.5 All statistical analyses were performed with SPSS 13.0 statistical software package.Results: 1 In normal ovarian tissue, benign ovarian tumor, borderline ovarian tumor and ovarian carcinoma, positive expression rate of YKL-40 protein was 0%, 20%, 50%, 80%, respectively. The positive expression rate in ovarian carcinoma group was significantly higher than the normal ovarian and benign ovarian tumor groups (P<0.0071). The positive express- ion rate of the borderline ovarian tumor and ovarian carcinoma was no statistically difference, but the YKL-40 expression (staining percentage scale) was higher in the ovarian tumor than in the borderline tumor (P=0.024). The positive expression rate of YKL-40 protein was no statistically significant difference in normal ovarian tissue, benign ovarian tumor and borderline ovarian tumor.2 In serous cystadenocarcinoma and mucinous cystaden- carcinoma, the positive expression rate of YKL-40 protein was 84% and 60%. The positive expression rate of the two path- ological types was no statistically significant difference.The positive rate in well differentiation group (87.5%) and in moderately-poorly differentiation group (77.27%) was no statis- tically significant difference (P>0.05). In ovarian carcinoma patients, the positive expression rate at early stages (stageⅠ,Ⅱ, 42.86%) was significantly lower than the advanced stages (stageⅢ,Ⅳ, 91.30%) (P<0.05). YKL-40 expression positively correlated with FIGO stage in tissue of ovarian carcinoma (rs=0.572,P=0.001).3 In healthy women, benign ovarian tumor, borderline ovarian tumor, preoperative ovarian carcinoma, the serum YKL-40 median levels were 35.56, 41.42, 44.34, 130.25(μg/L) respectively. The HE4 median levels were 41.10, 43.98, 65.21 and 260.90 (pmol/L). The median preoperative YKL-40 and HE4 value of ovarian carcinoma group were significantly higher than each of the former three groups respectively (P<0.05). The former three groups were further compared, no statistically significant difference respectively (P>0.05). In ovarian carcinoma group, the median postoperative YKL-40, HE4 levels were 58.57 and 124.32, the levels of preoperative were significantly higher than postoperative (P<0.05).4 In ovarian carcinoma group, the YKL-40 level of preoperative positively correlated with stage, the concentration of CA125 and YKL-40 protein expression in tissue. No correlation was found between serum YKL-40 and pathological types, grade, age. The preoperative serum HE4 level was associated with pathological types, the concentration of CA125 and age, wasn't correlated with FIGO stage, grade and serum YKL-40 concentration.5 when ovarian malignancy was compared with controls having healthy women, benign tumor, healthy women and benign tumor groups, the YKL-40 assay in receiver operating characteristic-area under the curve (ROC- AUC) was 0.931, 0.910, 0.917 respectively, the HE4 assay in ROC-AUC was 0.971, 0.954, 0.960 respectively. The diagnosis efficiency was the best when the YKL-40 assay and HE4 assay at the level of 69.20μg/L and 107.15pmol/L which were determined in ROC curve with controls having benign diseases and healthy women groups.6 When YKL-40 set point of 69.2 ug/L, CA125 set point of 35KU/L, regardless of the point value of HE4, the sensitivity of diagnosis was no statistically difference when YKL-40, HE4, CA125 was assayed alone. Combined assay was better than CA125 alone, and wasn't better than YKL-40, HE4 alone. The sensitivity of diagnosis is no statistically difference when any two or three assay combined. In early-stage ovarian cancer, the HE4 sensitivity of diagnosis is 100%.7 When HE4 set point of 107.15pmol/L and 150pmol/L, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value was no statistically significant difference(P>0.05).Conclusions: 1 The expression of YKL-40 protein is up-regulated in tissue of patients with epithelial ovarian carcinoma. The changes of their expression positively correlated with clinical pathology stage and preoperative YKL-40 level. Serum YKL-40 level can represent the expression of YKL-40 protein in tissue, the YKL-40 may participate the epithelial ovarian tumorous genesis and progression.2 The preoperative YKL-40,HE4 level cou1d be seen as markers for screening of the ovarian carcinoma. No correlation is found between serum YKL-40 and HE4, so they are complementary in screening the ovarian carcinoma. the serum YKL-40,HE4 are both correlated with serum CA125, so they can improve the diagnosis efficiency of CA125.3 The postoperative YKL-40 and HE4 level may be markers of evaluating the effect of surgery and monitoring patient's condition.4 The diagnosis efficiency of HE4 alone is better than YKL-40 alone. Combined assay is better than CA125 alone. The diagnosis value of YKL-40 and HE4 is higher than CA125. Three assay isn't better than any two assay combined.The YKL-40 and HE4 assay is advantageous for diagnosing early-stage ovarian cancer, combined with CA125 could improve the diagnosis rate.5 The set point of 107.15pmol/L is advantageous for the improving the diagnostic sensitivity, accurate, reducing the omission diagnostic rate. While the set point of 150pmol/L is advantageous for decreasing the mistake diagnostic rate.