CA125 Expression Levels Research Articles

Carbohydrate antigen 125 on epicardial fat and its association with local inflammation and fibrosis-related markers

BackgroundCarbohydrate antigen 125 (CA125) is a proteolytic fragment of MUC-16 that is increased in heart failure (HF) and associated with inflammation, fluid overload, and worse adverse events. Our main objective was to study the expression of CA125 on epicardium and its association with inflammation, adipogenesis, and fibrosis.MethodsEpicardial fat biopsies and blood were obtained from 151 non-selected patients undergoing open heart surgery. Immunohistochemistry, ELISA, or real-time PCR were used for analyzing protein or mRNA expression levels of CA125 and markers of inflammatory cells, fibroblasts, and adipocytes. Epithelial or stromal cells from epicardium were isolated and cultured to identify CA125 and its association with the adipogenesis and fibrosis pathways, respectively.ResultsThe median age was 71 (63–74) years, 106 patients (70%) were male, and 62 (41%) had an established diagnosis of HF before surgery. The slice of epicardial fat biopsy determined a positive and colorimetric staining on the epithelial layer after incubating with the CA125 M11 antibody, providing the first description of CA125 expression in the human epicardium. Epicardial CA125 showed a strong and positive correlation with markers of inflammation and fibrosis in the epicardial fat tissue while exhibiting a negative correlation with markers of the adipogenesis pathway. This relationship remained significant after adjusting for potential confounders such as a prior HF diagnosis and plasma CA125 levels.ConclusionEpicardial cells express CA125, which is positively associated with inflammatory and fibroblast markers in epicardial adipose tissue. These results suggest that CA125 may be biologically involved in HF progression (transition from adipogenesis to fibrosis).Graphical

MUC-16, tumour and congestive heart failure marker, is expressed on epicardial mesothelial cells and is inversely associated with epicardial fat genesis

Abstract Background CA-125 or mucin-16 (MUC-16) is a protector protein on epithelial luminal surfaces against physical stress through hydration process. However, some evidence suggests a role in fibrogenesis. MUC-16 can be detected in plasma after proteolytic cleavage with a predictive value for heart failure progression. Our main objective was to study the expression levels of this glycoprotein on epicardial mesothelial cells, its association with epicardial fat genesis, and biochemical markers. Methods and results We have used epicardial and subcutaneous fat from patients(n = 29) undergoing open heart surgery under informed consent and after approval by Ethics Committee. MUC-16 expression levels were detected on formalin-fixed paraffin-embedded epicardial fat biopsies with CA-125 antibody or real-time PCR on stored biopsies (n = 18) at -80ºC. Epicardial cells scraped with a scalpel were cultured and their MUC-16 expression was confirmed with a specific antibody and secondary fluorescent antibody. Primary cultures from epicardial stromal cells of 8 patients were obtained with collagenase digestion. After 15 days, adipogenesis was induced for 15 days with an adipogenic cocktail. Adipogenesis (AdipoQ) and mesothelial (ITLN-1) markers were quantified by real-time PCR on cells with and without adipogenesis. CA-125 expression levels were analyzed by real time-PCR on epicardial fat from 18 patients, as well as inflammation, fibrosis, stretch and adiposity markers levels on plasma by multiplex assay. Our results showed that MUC-16 is localized on epicardial mesothelial cells but not on adipocytes. The MUC-16-stained cells can be cultured and isolated after scraping the epicardium. The isolated epicardial stromal cells with collagenase showed a positive relationship between mesothelial maker (ITLN-1) and CA125 (Figure below). The higher presence of MUC-16 levels was inversely associated with AdipoQ after adipogenesis induction. From 8 plasma studied proteins, thrombospondin-2 (TP-2), was the best associated protein with MUC-16 on epicardial fat (r = 0,472; p = 0,48). Conclusion Epicardial cells express MUC-16. These types of cells can be isolated and cultured for studying their cleavage regulation and modulation. Epicardial stromal cells with a higher percentage of MUC-16 reduce the epicardial fat genesis. Further studies are needed for finding the main circulating plasma levels associated with epicardial MUC-16.

Effects of five prescriptions in Synopsis of Golden Chamber on the malignant phenotype and expression of CA125, CEA, HE4 proteins in human ovarian cancer cells.

e17546 Background: Ovarian cancer(OC) is a common gynecological tumor with characteristics of low early diagnosis rate, late lack of effective treatment and high mortality. It is an important problem to find new effective treatment for ovarian cancer. Synopsis of the Golden Chamber is the miscellaneous diseases part of Treatise on Typhoid and Miscellaneous Diseases written by Zhang Zhongjing, a famous medical expert in Eastern Han Dynasty of China, and is also the earliest classical treatise on diagnosis and treatment of miscellaneous diseases, which records 205 prescriptions. This study aims to screen out formula with strong inhibitory effects on OC from 205 prescriptions of Synopsis of the Golden Chamber , and investigate the effects of screened prescriptions in Synopsis of the Golden Chamber on human ovarian cancer cell malignant phenotype and CA125, CEA and HE4 proteins expression. Methods: MTT method was applied to screen out the best effective prescription and determine the IC50 value of prescription on ovarian cancer ES-2 and OV-1063 cells. The effects of screened prescriptions on the proliferation, migration, invasion, cloning ability, cell cycle and CA125, CEA and HE4 proteins expression of ES-2 and OV-1063 cells were investigated by MTT assay, RTCA assay, soft agar assay, flow cytometry and western blot analysis. Results: Guizhi Fuling Pill, Dachaihu Decoction, Xuanfuhua Decoction, Baitouweng Decoction and Bentun Decoction were screened out, which all could obviously inhibit the proliferation of ES-2 and OV-1063 cells with dose-effect and time-dependent manner. The IC50 values of Guizhi Fuling Pill, Dachaihu Decoction, Xuanfuhua Decoction, Baitouweng Decoction and Bentun Decoction for ES-2 cell were 636.476, 315.859, 24.357, 9.519, 96.533μg/ml respectively; for OV-1063 were 403.119, 225.176, 12.977, 9.256, 115.86μg/ml respectively. The five prescriptions all significantly affected the cell morphology, proliferation, migration, invasion, cloning ability, cell cycle of ES-2 and OV-1063 cells. The five prescriptions all could decreased the protein expression levels of CA125 and CEA in ovarian cancer OV-1063 cells, while Guizhi Fuling Pill, Dachaihu Decoction, Xuanfuhua Decoction and Baitouweng Decoction decreased the expression of HE4 protein in OV-1063 cells. Conclusions: The five prescriptions in Synopsis of the Golden Chamber can inhibit the malignant phenotype of ovarian cancer, which may be related to the inhibition of CA125, CEA and HE4 proteins expression.

Multiple Tumor Markers Detection for Correlation Diagnosis of Ovarian Cancer

The contents of serum CA125, alpha-fetoprotein (AFP) and CA199 and their diagnostic value in ovarian cancer were analyzed in this study. Firstly, 80 patients with ovarian malignant tumors from June 2019 to June 2020 in our hospital were included in the study group, and 80 patients with benign ovarian tumors were included in the control group during the same period. Serum levels and positive rates of CA125, AFP and CA199 were detected in both study group and control group. The expression levels of CA125, AFP and CA199 in the study group were all higher than those in the control group (P <0.05). The positive rate of AFP, CA199 and CA125 was 33.75%, 47.50% and 91.25% in study group, respectively. The joint detection positive rate was 92.50%. However, . The positive rate of CA125, AFP and CA199 was 23.75%, 0% and 11.25% in control group, and the joint detection positive rate was 28.75%. The positive rates of all indexes and the positive rates of comprehensive detection in the study group were higher than that in the control group (P < 0.05). Therefore, serum CA125, AFP and CA199 can be used as important indicators for the diagnosis of ovarian cancer.

Serum concentration of sex hormone-binding globulin in healthy volunteers and patients with breast cancer stratified by sex and age.

The objective of the present study was to compare sex hormone-binding globulin (SHBG) levels according to sex (healthy male and female volunteers) and age to determine reference values. Serum SHBG expression levels in patients with breast cancer with different tumor burden states were also determined. A total of 109 samples were obtained from 34 patients in 3 different disease states (non-tumor, localized tumor and systemic metastasis) during follow-up. A sandwich ELISA was conducted to measure SHBG, cancer antigen (CA)15-3 and CA125 expression levels. Wilcoxon rank-sum tests were performed on non-normally distributed data and an unpaired t-test was used for normally distributed variables. SHBG expression levels were higher in females compared with males (P<0.0001). When SHBG expression levels were compared by sex, the difference was maintained in the age groups <30, 30–39 and ≥50 years, but not in the 40–49 years group. In males, SHBG expression levels increased until the age of 49 and then decreased (P=0.01). In females, SHBG expression levels exhibited a decreased trend until the age of 49 (P=0.66). In patients with breast cancer, the SHBG expression levels revealed a decreasing trend after the age of 50, which was different compared with the healthy females. There was a decreasing trend of SHBG expression levels from pre-menopause to post-menopause healthy volunteers (P=0.74). CA15-3 (r2=0.07; P=0.59) and CA 125 (r2=−0.18; P=0.17) levels did not exhibit any significant correlation with SHBG expression levels. There was a significant difference in the SHBG expression levels between male and female healthy volunteers. SHBG expression levels also revealed different patterns between healthy female volunteers and female patients with breast cancer ≥50 years of age. The present study demonstrated that SHBG does not have value as a biomarker, but different reference values according to age and sex may aid in predicting high-risk groups for hormone-dependent cancer and guide treatment direction for post-menopausal breast cancer.

Glucose restriction combined with chemotherapy decreases telomere length and cancer antigen-125 secretion in ovarian carcinoma.

Although chemotherapy is the standard treatment for ovarian cancer (OC), recent studies have focused on its coupling with hypoglycemic drugs to decrease glucose availability. Similarly to cancer antigen 125 (Ca-125), telomerase, the key protein for telomere lengthening, is overexpressed in 90% of OC cases. The aim of the present study was to investigate the effect of the combination of glucose restriction and chemotherapy on telomere length and Ca-125 secretion in OC cells. SKOV-3, OVCAR-3 and Igrov-1 cells were treated with 20 µM cisplatin and 100 nM paclitaxel for 48 h in three different glucose concentrations: i) 4.5 g/l, ii) 1 g/l and iii) 0.5 g/l. The same treatment was repeated once per week for 6 consecutive weeks. The surviving cells were considered platinum-taxane escape (PTES) cells. The expression levels of telomerase and Ca-125 in treated and PTES cells were quantified by qPCR, and Ca-125 secretion by ELISA. Telomere length was evaluated by qPCR according to the Cawthon method. The modulation of Ca-125 by telomerase was assessed using inhibitors, small interfering RNA and transfection with human telomerase reverse transcriptase (hTERT) vectors. The implication of phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR) in Ca-125 modulation was investigated using specific inhibitors. An increase in hTERT and Ca-125 expression levels (range, 1.5–3 fold) was observed in short-term treated cells. However, an opposite effect was detected in PTES cells, where the rate of decrease in the expression levels of hTERT and Ca-125 reached 60% after treatment in 0.5 g/l glucose. Moreover, telomere length was decreased by 30% in cells treated with 0.5 g/l glucose. Inhibition of hTERT expression significantly decreased Ca-125 secretion, suggesting a potential modulation of Ca-125 by hTERT. The inhibition of the PI3K/Akt/mTOR pathway also decreased Ca-125 secretion; however, the effect of this treatment was not enhanced when coupled with telomerase inhibitors. In conclusion, the combination of chemotherapy and glucose restriction was observed to decrease Ca-125 secretion and telomerase expression leading to shortening in telomere length. Thus, decreasing glucose availability for OC cells during treatment may lead to a better clinical outcome and potentially improve the prognosis of patients with OC.

Abstract 639: Salt-inducible kinase 3 expression identifies long-term survivors of serous ovarian cancer

Abstract Background: Epithelial ovarian cancer (EOC) has a high tumor-associated mortality rate among the gynecological cancers because EOC is usually diagnosed during the advanced stage. Cancer antigen (CA) 125 is the most well-studied biomarker for ovarian cancer screening. However, CA125 is also elevated in numerous conditions, resulting in decreased specificity. Materials and Method: We collected ovarian cancer specimens from 204 patients and examined the SIK3 and CA125 expression levels. The expression percentage of SIK3 or CA125 in the tumor cells, pre-surgery serum CA125 was divided into two groups and compared with patient overall survival, progression-free survival, cancer stage, cancer type and chemotherapeutic resistance. Results: A total of 30.9% of the patients had stage I disease, 7.8% had stage II disease, 52.4% had stage III disease, and 8.9% had stage IV disease. The median OS and PFS were 49.5 months (range 0.25-205 months) and 28.4 months (0.25-182.4), respectively. The mean age of the patients was 52.8 years (range 25-82 years). The histological classification was based on the four main ovarian cancer types: serous (51.5%), endometrioid (14.2%), clear cell (20.6%), and mucinous (9.3%). In all stages of the disease, high expression of SIK3 (SIK3-H) was associated with a markedly better OS, compared with low expression of SIK3 (SIK3-L) (127.0 months and 46.0 months, respectively; hazard ratio [HR] for death, 0.59; 95% confidence interval [CI], 0.41 to 0.86; P=0.005). SIK3-H had a markedly better PFS rate than SIK3-L (66.0 months and 26.0 months, respectively; HR for disease progression or recurrence, 0.68; 95% CI, 0.47 to 0.99; P=0.04). The same results were evident for serous ovarian cancer, where SIK3-H had a better OS rate than SIK3-L (75.0 months and 34.0 months, respectively; HR for death, 0.57; 95% CI, 0.36 to 0.91; P=0.02) and a better PFS rate than SIK3-L (44 and 13 months, respectively; HR, 0.52; 95% CI, 0.32 to 0.83; P=0.006). Notably, for advanced stage serous ovarian cancer, Only SIK3-H had a better OS rate than SIK3-L (48.0 months and 28.0 months, respectively; HR for death, 0.56; 95% CI, 0.33 to 0.96; P=0.03) and PFS rate (32 and 13 months, respectively; HR, 0.57; 95% CI, 0.34 to 0.95; P=0.03). Tissue CA125 expression and the pre-surgery serum CA125 level did not show significant differences in OS and PFS. Our results demonstrated that high SIK3 expression correlated with better OS and PFS rates in ovarian cancer patients, especially in patients with advanced serous ovarian cancer. Conclusion: High expression of SIK3 indicates a better prognosis in primary ovarian cancer and serous disease, especially in advanced serous disease. Citation Format: Keng-Fu Hsu, Yu-Ling Liang, Chin-Han Wu, Neng-Yao Shih. Salt-inducible kinase 3 expression identifies long-term survivors of serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 639.

The clinical significance of the combined detection of serum Smac, HE4 and CA125 in endometriosis-associated ovarian cancer.

This study aims to investigate the clinical significance of serum Smac, HE4 and CA125 alone or combined for detecting endometriosis-associated ovarian cancer (EAOC). The level of serum Smac, HE4 and CA125 in 40 healthy controls, 40 cases of benign endometriosis ovarian tumor, and 60 cases of EAOC were detected by ELISA and electrochemical immune method. Serum Smac expression level was significantly lower in the EAOC group than in the control group and benign ovarian tumor group (P< 0.05), while HE4 and CA125 expression levels were significantly higher in the EAOC group than the other two groups. The sensitivity of Smac single detection was up to 91.67%, and the specificity of HE4 was up to 98.75%. Furthermore, the sensitivity of Smac + HE4 + CA125 combined was the highest, which reached up to 98.33%; but the specificity was low, which reached up to 75%. The serum expression level differences before and after surgery were statistically significant. As the number of chemotherapies increases, the Smac level increased, and HE4 and CA125 levels gradually decreased. Furthermore, Smac increased to normal at the end of the 2nd period of chemotherapy, while HE4 and CA125 decreased to normal in 2nd and 3rd period of chemotherapy, respectively. Serum Smac, HE4 and CA125 may play an important role in predicting EAOC and in monitoring the prognosis of postoperative EAOC.

MicroRNA-466 with tumor markers for cervical cancer screening.

Cervical cancer is the second most common cancer in women in the world. In this study, we explore tumor markers and microRNA-466 combination for cervical cancer screening. Tumor markers were measured by the methods of electro-chemiluminescent immunoassay and enzyme immunoassay. The microRNA-466 was performed by quantitative real-time polymerase chain reaction. Among normal group, hyperplasia group and cancer group, the CEA expression levels were 2.26 ng/ml, 3.85 ng/ml and 16.08 ng/ml, respectively. While the CA125 expression levels were 13.61 u/ml, 27.32 u/ml and 44.93 u/ml, respectively. The SCCA expression levels were 13.61 ng/ml, 27.32 ng/ml and 44.93 ng/ml, respectively. The expression levels of tumor markers were all gradually increased with the development of cervical lesions. The expression levels of microRNA-466 in cervical cancers (0.62) were greater than that in normal (0.076) and hyperplasia (0.24). The expression of microRNA-466 was correlated with lymphnode metastasis (P=0.000). There is a lower overall survival rate of patient with large tumor or lymphnode metastasis. Thus, the combination of tumor markers and microRNA-466 can be useful for early detection of cervical cancer and indicators for advanced stage and prognosis of the disease.

Expression of CA125 and cisplatin susceptibility of pleural effusion-derived human lung cancer cells from a Thai patient

Advances in understanding lung cancer biology and tumor markers aid clinicians in managing the disease. Cancer-associated antigen (CA)125 has garnered increasing attention in lung cancer research and may benefit the treatment and follow-up of this type of cancer. In Thai lung cancer patients, knowledge regarding ethnic differences in cancer cell biology is largely absent. We generated lung cancer cells from the pleural effusion fluids of a Thai patient and designated these as P1 cells. P1 cells were assessed for growth rate, response to chemotherapy, and the presence of tumor markers, in particular CA125 expression. Results of immunofluorescence indicated that P1 cells exhibited strong expression levels of CA125, comparable to that of established H460 lung cancer cells. Furthermore, P1 cells were analyzed for the expression of additional markers. Results revealed that H460 cells exhibited strong immunofluorescent signals from cytokeratin-19 fragments (CYFRA 21-1) and squamous cell carcinoma antigen (SCCA) while P1 presented only CYFRA 21-1 signals. We also found evidence of relative cisplatin resistance in P1 compared to the susceptibility level of established lung cancer cells. Thus, the results and methodology described in this study may aid the development of lung cancer diagnostic and therapeutic approaches and, in particular, advance understanding of ethnic differences.

Abstract 900: Tissue CA125 expression levels as a biomarker of endometrial cancer

Abstract Serum CA125 has been recognized as a biomarker of gynecological tumors. However, serum CA125 detection is not very sensitive and specific in the diagnosis of cervical and endometrial carcinoma. This study has investigated the endometrial CA125 expression in patients with endometrial polyps, hyperplasia and carcinoma in comparison with normal endometrium. A total of 242 subjects were recruited into this study and they were classified into six groups, namely proliferative phase endometrium (n = 24), secretory phase endometrium (n = 21), non-functional endometrial polyps (n = 24), simple hyperplasia (n = 24), complex hyperplasia (n = 26), and endometrial carcinoma (n = 126). An immunohistochemistry method was used to detect endometrial CA125 expression. The results showed that there were significant differences in CA125 levels between normal and diseased endometrium, with significantly increased CA125 expression in patients with endometrial polyps, complex hyperplasia, and carcinoma compared to those with normal endometrium. There was only a weak CA125 expression in normal endometrium and simple endometrium hyperplasia. There were significant differences in CA125 expression levels between patients with non-functional endometrial polyps, simple hyperplasia, and complex hyperplasia (χ2 = 9.652, p &amp;lt; 0.005). In endometrial carcinoma group, there was a significant difference in CA125 expression among patients with pathological grade I, II and III of endometrial carcinoma (χ2=11.975, p &amp;lt; 0.01), while there was no significant difference in CA125 expression between grade I and grade II carcinoma (χ2=3.698, p &amp;gt; 0.05). These findings indicate that endometrial CA125 expression can be used as a reliable biomarker in the diagnosis and clinical staging of endometrial carcinoma in Chinese women. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 900. doi:10.1158/1538-7445.AM2011-900

Abstract 2739: Claudin-3 expression is up-regulated in epithelial ovarian cancer tissues, including tumors with minimally elevated levels of CA125

Abstract Background: Epithelial ovarian cancer (EOC) is a leading cause of death from gynecological malignancies in the US. The high mortality rate associated with EOC is largely due to the late disease stage at which the majority of women present clinical symptoms. CA125 (MUC16) is a serum marker used for detection of ovarian cancer. Serum CA125 is elevated in the majority of women with ovarian cancer, but its clinical usefulness is limited in part by low sensitivity for detection of early stage disease. Therefore, biomarkers that specify early stage ovarian cancer are needed. Objective: To identify markers that improve upon the performance of CA125, we searched for genes that were increased in tumors expressing only low levels of CA125 mRNA. We reasoned that such biomarkers may have utility in detecting the early stage ovarian cancers that are missed by screening for serum CA125 alone. Methods: The expression levels of CA125 and additional candidate biomarkers were measured using real-time quantitative RT-PCR across a panel of normal ovary tissue specimens and epithelial ovarian tumors. Biomarker protein levels in normal ovary and ovarian tumor tissue extracts were assessed by immunoblotting. Results: CA125 mRNA levels were characterized across a panel of 27 normal ovary specimens and 96 epithelial ovarian tumors. In 78% of the ovarian tumor tissues, levels of CA125 transcript were elevated greater than 10-fold relative to the average expression measured in the normal ovary specimens. In the remaining 21 EOC specimens, CA125 mRNA levels were much more modestly elevated, with increased expression measuring less than 10-fold relative to the normal ovarian tissues. Claudin-3 (CLDN3) was identified as a biomarker whose transcript level was elevated greater than ten-fold in 90% of EOC tissues including the subset of ovarian tumors expressing only modestly elevated levels of CA125 mRNA. In 17 of the 21 tumor specimens exhibiting only modestly elevated CA125 message (81%), CLDN3 transcript was up-regulated greater than 10-fold. CLDN3 message was up-regulated over 100-fold in 11 of these 21 specimens (52%). Eleven of the 21 tumors with low CA125 mRNA and high CLDN3 mRNA were diagnosed at an early stage (stage 1 + 2). This increased expression of CLDN3 mRNA in ovarian tumor tissues displaying only slightly elevated CA125 transcript was confirmed by immunoblotting tumor tissue lysates with a monoclonal antibody specific for CLDN3. Conclusion: The elevated expression of CLDN3 mRNA and protein in epithelial ovarian cancer tissues exhibiting only modest up-regulation of CA125 suggests that CLDN3 may complement CA125 as a biomarker for detection and management of ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2739.

Abstract 818: Correlation of mRNA and protein expression of CA125 and HE4 in ovarian cancer tissues using real-time RT-PCR and reverse phase protein array technologies

Abstract BACKGROUND: Epithelial ovarian cancer is the fifth most frequent cause of cancer deaths among women in the United States. Prognosis is improved when it is detected in early stages but poor as the disease progresses. Monitoring for ovarian cancer currently uses the serum marker CA125, although it is not very effective in detecting early stage ovarian cancers. Recently, the biomarker HE4 has shown clinical utility in the detection of ovarian cancer. However, it is likely that additional markers are needed to detect early stage ovarian cancer. OBJECTIVE: This study investigated whether reverse phase protein array (RPPA) technology would complement real time RT-PCR and serve as an additional tool to screen for biomarkers. RPPA is a sensitive, high throughput, quantitative assay that measures small amounts of proteins simultaneously on a single slide. METHODS: The mRNA expression levels of CA125 and HE4 were measured using real-time quantitative RT-PCR from 27 normal ovary tissue specimens and 54 epithelial ovarian tumors. The protein levels for these biomarkers were assessed in tissue lysates from the same normal ovary and ovarian tumor specimens by immunoblotting and reverse phase protein arrays. RESULTS: CA125 mRNA was elevated in 76% (41/54) of the tumors at levels greater than 10 fold relative to the average expression in normal ovary tissue. Fifty-nine percent (32/54) of epithelial tumors expressed CA125 mRNA at greater than 100 fold compared to normal ovarian tissue. HE4 mRNA was over expressed in 84% (42/50) of the tumors at levels 10 fold greater and in 68% of the tumors at 100 fold greater than the average normal ovary tissue. Protein expression levels of the CA125 and HE4 biomarkers were measured by immunostaining tissue lysates on RPPAs. As observed for CA125 and HE4 mRNAs, there were statistically significant differences in the protein levels detected between normal ovary and ovarian tumor for both biomarkers. CA125 protein was detected in 81% of tumors at 2.5 fold greater than, and in 75% of the tumors at 5 fold greater than, the average of the normal ovary tissue. Seventy-seven percent of tumors had HE4 protein detected at levels greater than 2.5 fold and 30% greater than 5 fold compared to normal ovary tissue. Immunoblotting validated the RPPA results for HE4 protein expression in a subset of the tissue lysates. Importantly, a significant correspondence between the mRNA and protein levels of each biomarker was demonstrated with correlation coefficients of 0.88 and 0.78 for CA125 and HE4, respectively. CONCLUSION: In this dataset, there is a robust correlation between mRNA and protein levels for HE4 and CA125. As RPPA yielded similar results compared to immunoblotting, is quantitative, and has higher throughput, RPPA is a valuable method for high throughput analysis of protein expression in tissue lysates. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 818.

CA125 expression pattern, prognosis and correlation with serum CA125 in ovarian tumor patients

To determine the CA125 tissue expression levels in borderline and invasive epithelial ovarian tumor tissues. Secondly, to evaluate whether CA125 tissue expression levels correlate with clinico-pathological parameters and serum CA125 levels and finally to investigate the prognostic value of tissue CA125 expression levels in ovarian cancer (OC) patients. We designed tissue arrays (TA) and analyzed the CA125 expression in tissues from 778 Danish women with an ovarian tumor. Furthermore, corresponding preoperative blood samples obtained before surgery were collected from 382 women with OC. Significantly more CA125 expression positive tumors (no expression vs. expression) were found in the serous subtype compared to the percentage of positive tumors in mucinous, endometroid and other subtypes for patients both with borderline ovarian tumors and with OC (p<0.00001, p<0.00001). Similarly, a positive significant correlation was found between elevated serum CA125 levels and elevated levels of CA125 tissue expression (N=382 stage I-IV OC, Spearman rho=0.31, p<0.0001) (N=206 stage III OC, Spearman rho=0.30, p<0.0001). We found a significantly shorter survival for stage III/IV OC patients with no CA125 tissue expression compared to stage III/IV OC patients with positive CA125 tissue expression (p=0.0003). Our finding that tissue CA125 expression was lacking in late stage primary OC tumor of Danish women with poor survival may be of value in selecting patients as eligible candidates for individually based treatments.