Performance Of CA125 Research Articles

Characterization analysis of gut and bile microbiota for cholangiocarcinomas.

e16150 Background: Cholangiocarcinomas (CCAs), which derive from the epithelial cells of the biliary tree, constitute a serious and growing health problem worldwide. Gut and bile microbiota have not been characterized in patients with CCA, and better noninvasive diagnostic approaches for CCA are essential to be established. CA19-9 was the most commonly used tumor marker for CCA; nevertheless, the forecasting performance of CA19-9 remains unsatisfactory. The aim of this study was to investigate the characteristics of gut and bile microbiota combined with CA19-9 in CCA patients. Methods: Fecal samples were collected from 42 CCA patients (16 of the total with Bile samples) and 16 healthy normal controls (HNC). 42 CCA patients were divided into three group according to CA19-9 levels: CCN (CA19-9 negative),CCP (CA19-9 positive: CPL (CA19-9 positive within 10 times) and CPH (CA19-9 positive over 10 times)) groups. DNA was extracted from fecal and bile samples and subjected to 16S rRNA gene analysis. The correlation between gut microbiota and clinical data in CCA group were further analyzed with Spearman rank correlation analysis. Results: Comparing with HNC group, the relative abundance of Firmicutes and Actinobacteriota were significantly decreased, whereas Proteobacteria and Bacteroidota were significantly enriched in CCA group at phylum level (all P < 0.01). Interestingly, Firmicutes/Bacteroidota (F/B) ratio significant decreased in CCA group compared to HNC group(P < 0.05). CA19-9 were inversely correlated with Bifidobacterium, which in turn was associated with Klebsiella in CCA patients. Especially the relative abundance of Klebsiella in CCP group was significantly enriched than CCN group(P < 0.05). Conclusions: Our findings provide evidence supporting Klebsiella may serve as a non-invasive intestinal microbiomarker for CCAs. Combinating with CA19-9, Klebsiella may improve the diagnosis of CCAs as non-invasive approach. Bifidobacterium is likely to be a potential protective factor for anti-tumorgenesis of CCAs.

Ce-MOF/COF/Carbon Nanotube Hybrid Composite: Construction of Efficient Electrochemical Immune Platform for Amplifying Detection Performance of CA125

Ce-MOF/COF/Carbon Nanotube Hybrid Composite: Construction of Efficient Electrochemical Immune Platform for Amplifying Detection Performance of CA125

Serum-based assay for adnexal mass risk of ovarian malignancy.

5551 Background: A Deep learning neural network was developed to assess ovarian cancer risk in women presenting with adnexal mass into risk categories. The algorithm shows potential to improve on the performance of CA-125 as the standard biomarker to monitor women as a clinical management metric to trace increased risk of malignancy. Methods: Serum specimens from an enriched biobank (N = 2688) were collected during previous clinical studies from women presenting with an adnexal mass at risk of ovarian cancer. Protein biomarker data from these specimens were used to develop a novel neural network for binary stratification of ovarian cancer risk assessment. These specimens were divided between training and testing data sets using 5-fold cross validation during training. A randomized, separate sample set was withheld from use in training and testing the algorithm for independent validation purposes. As algorithm inputs seven biomarkers are used in the network: cancer antigen 125, human epididymis protein, beta-2 microglobulin, apolipoprotein A-1, transferrin, transthyretin, and follicle stimulating hormone. In addition to these biomarkers, the patient’s age and menopausal status are used. Menopause was defined as the absence of menses for ≥12 months. The algorithm uses supervised learning with known histopathology diagnoses as the labels for training. The algorithm is a classification deep feedforward neural network. The neural network is regularized using node dropout to reduce overfitting. The final layer of the neural network has two nodes and uses the softmax function to assign a binary classification of low or high-risk of malignancy. Results: Algorithm performance metrics are also shown comparing predicted results from the algorithm to the known malignancy diagnoses. The performance metrics are also compared below to the standard of care biomarker test, cancer antigen 125 (CA125), reporting increased sensitivity by 26.1%, and failure to reject the null hypothesis of equivalent specificity. Conclusions: The algorithm detected 91% of malignancies in the independent validation data. This high sensitivity in malignancy detection paired with the failure to reject the null hypothesis of equivalent specificity (Pearson’s chi-squared test p-value of 0.281) and negative predictive value (NPV) suggest the algorithm could be used two-fold. First, surgical referral to gynecological oncologists for women classified in the high-risk cohort. The second as a goal with future clinical validation, is that women with a low risk of malignancy might be able to delay surgery and enter into a serial monitoring clinical management care pathway.[Table: see text]

Abstract PR-010: Blinded and meta-analysis validation of an improved serological test for PDAC using the combination of CA19-9 and the sTRA glycan

Abstract Improvements in the clinical outcomes of pancreatic cancer patients may be achieved if physicians could identify the disease earlier. Recent studies demonstrated the promise of a biomarker panel is a simple combination between CA19-9 and another marker called sTRA, so named because it detects the sialylated version of the glycan bound by the TRA-1-60 (tumor-related antigen) antibody. The sTRA glycan is structurally related to the CA19-9 antigen and is produced by a different subtype of cancer cells than make CA19-9. We hypothesized that, among patients with PDAC, different patients have plasma elevations in CA19-9 than have plasma elevations in sTRA, and that as a result, a panel comprising the two markers detects more cancers at high specificity (low false-positive rate) than either marker alone. To test this hypothesis, we analyzed the relationships and biomarker performance of CA19-9 and sTRA across seven different datasets, encompassing 729 patient samples collected from four different clinical centers. We tested whether unique elevation occurred for each marker in each dataset, and whether the combination of markers performed better than then individual markers for distinguishing PDAC from healthy subjects and from benign pancreatic disease. We observed complementary elevations of sTRA or CA19-9 in the PDAC patients in each dataset. A two-marker panel composed of CA19-9 and sTRA and a three-marker panel composed of CA19-9 and two versions of the sTRA immunoassay gave statistically significant improvements over CA19-9 across the datasets for distinguishing PDAC from non-PDAC samples (healthy, chronic pancreatitis, pancreatic cyst, and biliary stricture/stones). At 95% specificity, sensitivity was improved from 36-55% across datasets for CA19-9 to 61-67% across datasets for the three-marker panel. The lead panel further showed 95% specificity and 61% sensitivity using blinded calls on another validation set (N = 340). This analysis serves as broad support for an improved serological test for PDAC using the combination of CA19-9 and sTRA. In light of this level of validation, the lead panel could be considered the most promising panel from the currently available information. If further validated using clinical assays, it may be good enough for surveillance among patients with increased risk for PDAC, in combination with follow-up modalities to establish diagnosis. Citation Format: Ying Liu, Ben Staal, Daniel Barnett, Zonglin He, Chongfeng Gao, Mark Hurd, Pamela Bartlett, Aatur Singhi, J. Bradley Morrow, Gregory Cote, Anirban Maitra, Ying Huang, Randall Brand, Brian Haab. Blinded and meta-analysis validation of an improved serological test for PDAC using the combination of CA19-9 and the sTRA glycan [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PR-010.

Improved early detection of ovarian cancer using longitudinal multimarker models

BackgroundOvarian cancer has a poor survival rate due to late diagnosis and improved methods are needed for its early detection. Our primary objective was to identify and incorporate additional biomarkers into longitudinal models to improve on the performance of CA125 as a first-line screening test for ovarian cancer.MethodsThis case–control study nested within UKCTOCS used 490 serial serum samples from 49 women later diagnosed with ovarian cancer and 31 control women who were cancer-free. Proteomics-based biomarker discovery was carried out using pooled samples and selected candidates, including those from the literature, assayed in all serial samples. Multimarker longitudinal models were derived and tested against CA125 for early detection of ovarian cancer.ResultsThe best performing models, incorporating CA125, HE4, CHI3L1, PEBP4 and/or AGR2, provided 85.7% sensitivity at 95.4% specificity up to 1 year before diagnosis, significantly improving on CA125 alone. For Type II cases (mostly high-grade serous), models achieved 95.5% sensitivity at 95.4% specificity. Predictive values were elevated earlier than CA125, showing the potential of models to improve lead time.ConclusionsWe have identified candidate biomarkers and tested longitudinal multimarker models that significantly improve on CA125 for early detection of ovarian cancer. These models now warrant independent validation.

Diagnostic value of detection of peripheral blood human telomerase reverse transcriptase mRNA and four tumor markers in patients with gastric cancer

Objective To evaluation the value of single and combined detection of peripheral blood human telomerase reverse transcriptase (hTERT) mRNA and tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 72-4 (CA72-4), CA19-9 and CA125 in the diagnosis of gastric cancer. Methods A total of 48 patients diagnosed with gastric cancer from June 2017 to October 2018 in Baotou Tumor Hospital were enrolled in the study group. Fifty healthy subjects were selected as healthy control group. The peripheral venous blood samples were collected from all subjects. After the synthesis of hTERT cDNA by reverse transcription, real-time fluorescence quantitative polymerase chain reaction (RT-PCR) was used for the amplification of hTERT gene fragment. The tumor markers CEA, CA72-4, CA19-9 and CA125 were quantitatively detected by electrochemiluminescence instrument. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of individual markers or joint detection were calculated. The sensitivity and specificity of joint testing items were compared. Results There were statistically significant differences in the positive rates of hTERT mRNA (P 0.05). The expression of hTERT mRNA was correlated with TMN stage, lymph node metastasis and distant metastasis (all P 0.05). The results of diagnostic indices showed that the hTERT mRNA had high sensitivity (84.8%), specificity (82.7%), accuracy (83.7%), positive predictive value (81.2%) and positive likelihood ratio (4.90). CA72-4 also had high specificity (61.2%), accuracy (64.3%), and positive predictive value (45.8%), which were second only to the hTERT mRNA. The diagnostic performance of CA125 combined with CEA, CA72-4, CA19-9 and peripheral blood hTERT mRNA was not significantly different from the latter four combined detection (P > 0.05). The sensitivity and specificity of combined detection of traditional tumor markers CEA, CA72-4 and CA19-9 were 62.5% and 80.0%. The sensitivity and specificity of combined detection of hTERT mRNA, CEA, CA72-4 and CA19-9 could be change to 90.0% and 67.5%. The difference in sensitivity between the two combined detection groups was statistically significant (P = 0.019), and the difference in specificity was not statistically significant (P > 0.05). Conclusion The comprehensive evaluation index of peripheral blood hTERT mRNA is better than the traditional gastric tumor markers, and it is expected to become a new marker for the diagnosis of gastric cancer. Key words: Stomach neoplasms; Diagnosis; Telomerase reverse transcriptase; Tumor markers, biological; Polymerase chain reaction

Abstract A04: Identification of novel pancreatic cancer-specific biomarkers with organoid models

Abstract Pancreatic ductal adenocarcinoma (PDA) is almost uniformly lethal and surgical intervention is the only cure. Unfortunately, the majority of patients are ineligible for resection because of the advanced stage of disease by the time of diagnosis. This is due in part to that lack of diagnostic tools, especially for families with elevated risk. Although considered an intractable and aggressive malignancy, progression from the initiating events to overt cancer requires approximately 12 years, and advancement to metastatic disease takes another 5 – 7 years. This latency indicates that there is a window for early detection and intervention. The PDA biomarker, CA19-9, is measured in the blood to follow tumor burden longitudinally, but is neither sensitive nor specific enough to be used for diagnosis. In particular, the use of CA19-9 in PDA diagnosis is problematic given the elevation of CA19-9 in benign conditions, such as pancreatitis, that have a higher incidence than PDA. To improve the diagnostic performance of CA19-9, we identified tissue- and cancer-specific protein carriers of the CA19-9 carbohydrate modification using murine and human organoid model systems of pancreatic cancer disease progression. To induce CA19-9 expression in murine organoids, two human gylcosyl transferases that were deficient in mice were ectopically expressed. CA19-9 protein carriers specific to malignancy were identified relative to normal, proliferating ductal cells. Some CA19-9 carriers that were shared between normal and malignant pancreatic ductal organoids were also detected in the sera of patients with benign pancreatic disease, highlighting their inability to distinguish malignancy from pancreatitis. Importantly, several of the tumor-specific novel CA19-9 carriers identified in organoids also discriminated between benign and malignant disease in human patient sera, and are nominated for clinical validation. Overall, organoid model systems allow identification of biomarkers that discriminate between normal proliferation and malignant conditions of multiple gastrointestinal tissues, providing a robust platform for biomarker discovery. Citation Format: Dannielle Engle, Herve Tiriac, Rivera Keith, Michael Ludwig, Chang-il Hwang, Kenneth Yu, Darryl Pappin, David Tuveson.{Authors}. Identification of novel pancreatic cancer-specific biomarkers with organoid models. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A04.

Cytokines as biomarkers of pancreatic ductal adenocarcinoma: A systematic review

Objectives A systematic review of the role of cytokines in clinical medicine as diagnostic, prognostic, or predictive biomarkers in pancreatic ductal adenocarcinoma was undertaken. Materials and Methods A systematic review was conducted according to the 2009 PRISMA guidelines. PubMed database was searched for all original articles on the topic of interest published until June 2015, and this was supplemented with references cited in relevant articles. Studies were evaluated for risk of bias using the Quality in Prognosis Studies tools. Results Forty one cytokines were investigated with relation to pancreatic ductal adenocarcinoma (PDAC) in 65 studies, ten of which were analyzed by more than three studies. Six cytokines (interleukin[IL]-1β, -6, -8, -10, vascular endothelial growth factor, and transforming growth factor) were consistently reported to be increased in PDAC by more than four studies; irrespective of sample type; method of measurement; or statistical analysis model used. When evaluated as part of distinct panels that included CA19-9, IL-1β, -6 and -8 improved the performance of CA19-9 alone in differentiating PDAC from healthy controls. For example, a panel comprising IL-1β, IL-8, and CA 19–9 had a sensitivity of 94.1% vs 85.9%, specificity of 100% vs 96.3%, and area under the curve of 0.984 vs 0.925. The above-mentioned cytokines were associated with the severity of PDAC. IL-2, -6, -10, VEGF, and TGF levels were reported to be altered after patients received therapy or surgery. However, studies did not show any evidence of their ability to predict treatment response. Conclusion Our review demonstrates that there is insufficient evidence to support the role of individual cytokines as diagnostic, predictive or prognostic biomarkers for PDAC. However, emerging evidence indicates that a panel of cytokines may be a better tool for discriminating PDAC from other non-malignant pancreatic diseases or healthy individuals.

Abstract B20: Development and validation of diagnostic biomarker model for detection of early stage pancreatic cancer

Abstract Background: Although resectable pancreatic cancers are associated with better survival, only about 10% of pancreatic patients present with localized disease. Imaging modalities, notably endoscopic ultrasound and Magnetic resonance cholangiopancreatography, allow detection of early stage pancreatic cancer or small pancreatic cysts. However, these imaging modalities are not suitable for screening in terms of throughput, cost effectiveness, or invasiveness. Blood-based biomarkers could be ideal for screening of early stage pancreatic cancer. The performance of CA19-9 as a pancreatic cancer biomarker is limited and moreover CA 19-9 is not detectable in 5-10% of subjects with fucosyltransferase deficiency. As a result there is a need for additional markers that complement CA 19-9 for reliable detection of early stage pancreatic cancer. We have previously identified and obtained initial validation data for a set of blood based biomarkers which distinguished cases from control in the pre-diagnostic setting (Faca et al PLoS Medicine, 2008). We have undertaken further validation of this marker panel augmented with novel candidates including autoantibodies to tumor antigens identified by recombinant protein array. Methods: The selected biomarker candidates as well as CA19-9 were further assayed in a training set, consisting of plasmas from 138 pancreatic cancer patients and 81 controls (52 healthy subjects and 29 subjects with chronic pancreatitis) resulting in a combination rule which was tested in an independent cohort consisting of plasmas from 42 early stage pancreatic cancer patients, 50 healthy controls, 29 subjects with chronic pancreatitis, and 14 subjects with benign pancreatic cysts. Results: A logistic regression model was built in the training set using 5 markers. The AUCs of the model and CA19-9 alone were 0.80 (95% CI = 0.71-0.89) and 0.76 (95% CI = 0.67-0.86) (P value for difference in AUC = 0.014) in the training set. In the test set, the AUCs of the model in a comparison of early stage pancreatic cancer vs. (1) healthy controls, (2) subjects with chronic pancreatitis, and (3) subjects with benign pancreatic cysts were 0.91, 0.85, and 0.94 respectively. The marker panel substantially improved the negative predictive values (NPV) at 98% sensitivity in comparison of early stage pancreatic cancer vs. (1) healthy controls and (2) subjects with chronic pancreatitis (NPVs of the panel = (1) 0.96, (2) 0.95, and (3) 0.88; NPVs of CA19-9 alone = (1) 0.83, (2) 0.83, and (3) 0.88). Stratification based on CA19-9 positivity (cut off = 37 units/ml) yielded AUCs of (1) 0.79, (2) 0.72, and (3) 0.90, and NPVs were (1) 0.99, (2) 0.98, and (3) 0.95 in CA19-9 negative subjects. Conclusions: We have validated a marker combination with a potential to differentiate early stage pancreatic cancer from healthy controls, subjects with chronic pancreatitis and subjects with pancreatic cysts. Citation Format: Ayumu Taguchi, Michela Capello, Yang Zhao, Ingrid Babel, Gary Goodman, Margaret A. Tempero, Matthew A. Firpo, Matthew H. Katz, Ziding Feng, Samir Hanash. Development and validation of diagnostic biomarker model for detection of early stage pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B20.

OP0004 Testing AGR2 as an early cancer biomarker

Background The poor prognosis associated with ovarian and pancreatic cancer may be in part attributable to an absence of specific symptoms. The early detection of these tumours is therefore essential. AGR2 is reported to function in tumorigenesis, and thus has potential as a novel biomarker for early detection of cancer. The aims of this study were to evaluate AGR2 as a potential predictive marker of ovarian and pancreatic cancer either alone or in combination with other biomarkers. Methods A nested case–control study involving a total of 360 prediagnosis serum samples from 52 women with pancreatic and 49 women with ovarian cancer, also 145 non-cancer women participating in UKCTOCS, were assayed. The samples from pancreatic and ovarian cases were grouped according to time before diagnosis. AGR2, CA125, and CA19-9 concentrations were measured with ELISA or CLIA, or both. ROC curve analysis was done to establish the benefit of combining biomarkers. Findings AGR2 concentrations were not significantly higher in prediagnosis ovarian cancer cases compared with non-cancer controls (16.89 ng/mL and 16.94 ng/mL, respectively), although rose within cases towards diagnosis. For ovarian cancer, the area under the ROC curve (AUC) of CA125 (0.734) was not significantly improved by addition of AGR2 (0.752). AGR2 concentrations were significantly higher in pancreatic cancer cases compared with controls (18.22 ng/mL and 14.67 ng/mL, respectively). The AUCs of combined biomarker panels (AGR2 and CA19-9; AGR2, CA19-9, and CA125) were significantly higher than those of CA19-9 alone (0.75, 0.759, and 0.679, respectively). Interpretation AGR2 can be measured with ELISA in prediagnostic ovarian and pancreatic cancer serum samples. Despite its rise with cancer progression, AGR2 is a poor early marker for ovarian cancer because it adds little to CA125 performance. AGR2 in combination with CA19-9 and CA125 improves on the ability to detect pancreatic cancer before clinical diagnosis.

Measurement of Phospholipids May Improve Diagnostic Accuracy in Ovarian Cancer

BackgroundMore than two-thirds of women who undergo surgery for suspected ovarian neoplasm do not have cancer. Our previous results suggest phospholipids as potential biomarkers of ovarian cancer. In this study, we measured the serum levels of multiple phospholipids among women undergoing surgery for suspected ovarian cancer to identify biomarkers that better predict whether an ovarian mass is malignant.Methodology/Principal FindingsWe obtained serum samples preoperatively from women with suspected ovarian cancer enrolled through a prospective, population-based rapid ascertainment system. Samples were analyzed from all women in whom a diagnosis of epithelial ovarian cancer (EOC) was confirmed and from benign disease cases randomly selected from the remaining (non-EOC) samples. We measured biologically relevant phospholipids using liquid chromatography/electrospray ionization mass spectrometry. We applied a powerful statistical and machine learning approach, Hybrid huberized support vector machine (HH-SVM) to prioritize phospholipids to enter the biomarker models, and used cross-validation to obtain conservative estimates of classification error rates.ResultsThe HH-SVM model using the measurements of specific combinations of phospholipids supplements clinical CA125 measurement and improves diagnostic accuracy. Specifically, the measurement of phospholipids improved sensitivity (identification of cases with preoperative CA125 levels below 35) among two types of cases in which CA125 performance is historically poor - early stage cases and those of mucinous histology. Measurement of phospholipids improved the identification of early stage cases from 65% (based on CA125) to 82%, and mucinous cases from 44% to 88%.Conclusions/SignificanceLevels of specific serum phospholipids differ between women with ovarian cancer and those with benign conditions. If validated by independent studies in the future, these biomarkers may serve as an adjunct at the time of clinical presentation, to distinguish between women with ovarian cancer and those with benign conditions with shared symptoms and features.

Comparison of three malignancy risk indices and CA-125 in the preoperative evaluation of patients with pelvic masses

BackgroundPatients with pelvic mass are the most referred patients to gynecologist. The aim of this study was to evaluate the ability of three malignancy risk indices (RMI 1, RMI 2 and RMI 3) and CA-125 to discriminate a benign from a malignant pelvic mass in our region (North of Iran).MethodsThis retrospective study was performed on 182 women with pelvic masses referred to Yahyanejad Hospital from 2007 to 2009. Ultrasound scans were scored as one point for each of the following characteristics: multilocular cyst, solid areas, intra-abdominal metastases, ascites, and bilateral lesions. For each patient a total ultrasound score (U) was calculated. The difference of the three RMI was based on the allocation of the U and M scores. The sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) of level of serum CA-125, the RMI 1, 2 and 3 were compared.ResultsMean age of the patients was 39.9 ± 9.3 years. Most of them were premenopausal (161 women or 88.4%). A significant linear trend for malignancy was found by increasing age, ultrasound score, and serum CA-125. The best performance of CA125 was at a cut-off 88 U/ml, with a sensitivity of 88%, a specificity of 97%, a positive predictive value of 84%, and a negative predictive value of 99%. RMI 1 and 3 at the optimal cut off point of 265 and RMI2 at the optimal cut off point of 355, had a sensitivity of 91%, specificity of 96%, a positive predictive value of 78%, and a negative predictive value of 99%.ConclusionIn our population we found that there is no statistically significant difference in the performance of three malignancy risk indices (RMI 1, RMI 2, and RMI 3) and CA125 in differentiating between benign and malignant pelvic masses.

Reply: The performance of the risk of ovarian malignancy algorithm

Reply: The performance of the risk of ovarian malignancy algorithm

The performance of the risk of ovarian malignancy algorithm

The performance of the risk of ovarian malignancy algorithm

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.

Use of a novel biomarker HE4 for monitoring patients with epithelial ovarian cancer

5535 Background: The serum biomarker CA125 is effectively used for monitoring response to therapy and monitoring for recurrent disease in patients with epithelial ovarian cancer (EOC). However, CA 125 is not elevated in approximately 20% of patients. The novel tumor marker HE4 has been shown to be elevated in the majority of EOC patients as well as in patients that do not express CA125. The object of this study was to determine the concordance between HE4 and CA125 in patients being followed with EOC. Methods: This was a retrospective study utilizing serum samples obtained from an IRB approved serum bank. Serial samples from patients either undergoing treatment for EOC or being monitored for recurrence were obtained. Clinical status of the patients was assessed through serial CA125 and CT imaging with documentation of regression or progression of disease or absence of disease over time. Serum CA125 and HE4 levels were measured using the Architect CA 125II assay and the HE4 EIA assay. Serial changes in the serum CA125 and HE4 levels were compared to the documented clinical status using a cutoff of 25%. Concordance between HE4 and CA125 was determined and the performance of CA125 and HE4 was compared directly using a non-inferiority approach. Results: A total of 434 serial samples from 80 patients either undergoing treatment for EOC or being monitored for recurrence were obtained. Longitudinal analysis of the serum sample sets showed that changes in HE4 values were not inferior to changes in CA125 values in accordance with clinical status (p=0.039). CA125 correlated with clinical status in 78.8% (63/80) and HE4 correlated in 76.2% (61/80). In patients where CA125 did not correlate with clinical status, HE4 correlated in 23.5% (4/17). In patients where HE4 did not correlate with clinical status, CA125 correlated in 31.6% (6/19). In consideration of all cases either CA125 or HE4 correlated with clinical status for 83.8% (67/80). Conclusions: HE4 is a valuable biomarker for the majority of patients with EOC and behaves in concordance with CA125 in patients with EOC. As well, HE4 is a valuable marker for the management of some patients where CA125 is not of clincal utility. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Fujirebio Diagnostics, Inc Fujirebio Diagnostics, Inc, Thiel Statistical Consultants Fujirebio Diagnostics, Inc Fujirebio Diagnostics, Inc

The Quest for Ovarian Cancer's Holy Grail: Can CA-125 Still Be the Chalice of Early Detection?

The Quest for Ovarian Cancer's Holy Grail: Can CA-125 Still Be the Chalice of Early Detection?

Predictive values of serum tumour markers tetranectin, OVX1, CASA and CA125 in patients with a pelvic mass

Our objective was to compare the predictive value of the well-established tumour marker CA125 with the newer tumour markers tetranectin (TN), OVX1 and CASA in distinguishing benign and malignant pelvic masses in women. Participants included 185 women, 19 years or older, with a pelvic mass planned for surgical exploration. Significantly different CA125 levels were found between benign tumours and localised ovarian cancer (OC), advanced OC and other non-OCs. Significantly different TN levels were found between benign tumours and advanced OC (stage III/IV), between benign tumours and other cancers and between all OCs and other cancers. For CASA, significant differences were found between benign tumours and all OCs as well as advanced OC. No significant differences could be demonstrated for OVX1. Significant correlations for the 44 OC patients were found between CA125, TN and CASA. No significant correlations were found for OVX1, possibly because of the method used for collection and handling of serum samples. None of the new markers had any additional predictive value compared to CA125. TN and CASA levels correlated with FIGO stage and could be used to discriminate between benign and advanced OC. However, in comparison to the performance of CA125, the additional discriminative value of TN and CASA was minor.