CA125 Test Research Articles

The diagnostic performance of CA-125 for the detection of ovarian cancer in women from different ethnic groups: a cohort study of English primary care data

BackgroundCA-125 testing is a recommended first line investigation for women presenting with possible symptoms of ovarian cancer in English primary care, to help determine whether further investigation for ovarian cancer is needed. It is currently not known how well the CA-125 test performs in ovarian cancer detection for patients from different ethnic groups.MethodsA retrospective cohort study utilising English primary care data linked to the national cancer registry was undertaken. Women aged ≥ 40 years with a CA-125 test between 2010 and 2017 were included. Logistic regression predicted one-year ovarian cancer incidence by ethnicity, adjusting for age, deprivation status, and comorbidity score. The estimated incidence of ovarian cancer by CA-125 level was modelled for each ethnic group using restricted cubic splines.ResultsThe diagnostic performance of CA-125 differed for women from different ethnicities. In an unadjusted analysis, predicted CA-125 levels for Asian and Black women were higher than White women at corresponding probabilities of ovarian cancer. The higher PPVs for White women compared to Asian or Black women were eliminated by inclusion of covariates.ConclusionThe introduction of ethnicity-specific thresholds may increase the specificity and PPVs of CA-125 in ovarian cancer detection at the expense of sensitivity, particularly for Asian and Black women. As such, we cannot recommend the use of ethnicity-specific thresholds for CA-125.

The Yolk Sac Abnormalities, Maternal Serum Level of Cancer Antigen 125 (CA-125) and Beta Human Chorionic Gonadotropin (B-HCG) as an Early Predictors of First Trimester Pregnancy Loss in Patients with Threatened Miscarriage

Background: Pregnancy loss before 20 weeks is considered a miscarriage, as is the loss of a fetus weighing less than 500 grams before viability. A medical emergency, threatened miscarriage affects 15–25% of pregnancies. 
 Aim and objectives: The goal of this study was to assess the predictive value of maternal blood levels of Cancer Antigen 125 (CA-125) and beta-human chorionic gonadotropin (B- HCG) in individuals at risk of miscarriage during the first trimester. 
 Subjects and methods: This study was a prospective cohort study. This study included 120 pregnant women with threatened abortion between (6-11 weeks) and followed up till end of 14th week. Results: 36(30%) of pregnant women aborted, while 84(70%) of women continued till 14th weeks of pregnancy. At a cut-off value of 45 U/ml, the CA125 test was shown to have a sensitivity of 88.9% and a specificity of 77.5%, respectively, while also having a positive predictive value of 79.8% and a negative predictive value of 87.5%. At a cut-off value of 18.501 mlIU/ml, the B-HCG test's sensitivity and specificity were determined to be 96.3 and 88.9, respectively, with a positive predictive value of 89.7% and a negative predictive value of 96%. 
 Conclusion: Even before fetal morphology can be investigated sonographically, abnormalities in the size of the yolk sac can be utilized as a good prognostic sign of early pregnancy loss. Pregnancy viability can be estimated from first trimester serum CA 125 and Beta HCG measurements.

A real-world comparison of the clinical and economic utility of OVA1 and CA125 in assessing ovarian tumor malignancy risk.

Aim: This largest-of-its-kind study evaluated the clinical utility of CA125 and OVA1, commonly used as ovarian tumor markers for assessing the risk of malignancy. The research focused on the ability and utility of these tests to reliably predict patients at low risk for ovarian cancer. Clinical utility endpoints were 12-month maintenance of benign mass status, reduction in gynecologic oncologist referral, avoidable surgical interventionand associated cost savings. Materials& methods: This was a multicenter retrospective review of data from electronic medical records and administrative claims databases. Patients receiving a CA125 or OVA1 test between October2018 and September2020 were identified and followed for 12months using site-specific electronic medical records to assess tumor status and utilization outcomes. Propensity score adjustment was used to control for confounding variables. Payer allowed amounts from Merative MarketScan Research Databases were used to estimate 12-month episode-of-care costs per patient, including surgery and other interventions. Results: Among 290 low-risk OVA1 patients, 99.0% remained benign for 12months compared with 97.2% of 181 low-risk CA125 patients. The OVA1 cohort exhibited 75% lower odds of surgical intervention in the overall sample of patients (Adjusted OR: 0.251, p≤0.0001), and 63% lower odds of gynecologic oncologist utilization among premenopausal women (Adjusted OR: 0.37, p=0.0390) versus CA125. OVA1 demonstrated significant savings in surgical interventions ($2486, p≤0.0001) and total episode-of-care costs ($2621, p≤0.0001) versus CA125. Conclusion: This study underscores the utility of a reliably predictive multivariate assay for assessing ovarian cancer risk. For patients assessed at low risk of ovarian tumor malignancy, OVA1 is associated with a significant reduction in avoidable surgeries and substantial cost savings per patient. OVA1 is also associated with a significant reduction in subspecialty referrals for low-risk premenopausal patients.

Abstract 3333: Exosomal non-coding RNAs as a biomarker to improve early ovarian cancer detection

Abstract Purpose: There is no consensus on screening for ovarian cancer in high-risk women because no effective biomarker or screening method exists, especially for early-stage cancer patients. The available methods, such as monitoring of CA125 levels, transvaginal ultrasound, and combination of pelvic examination are associated with high false-positive results, leading to additional unnecessary imaging tests, emotional burdens, and risk of invasive surgery for women without cancer. An effective, reliable, and non-invasive method for early detection of ovarian cancer is thus critically needed. In this research, weThus, we aim to identify a distinctive signature of exosomal small RNAs to serve as a novel biomarker for detecting early-stage ovarian cancer in high-risk population. Methods: Women of all ages and ethnical backgrounds were included in this study. Blood samples were collected in the clinic from women with germline BRCA mutations. A total of 30 patients with ovarian cancer before surgery, and 30 age-matched (mean age = 55) healthy women as controls were used. Among the 30 thirty cases, 11 patients had early (stage I) ovarian cancer. Identification of differential exosome small non-coding RNA copy numbers in plasma samples from BRCA1 mutation carriers with and without ovarian cancer was performed by next-generation RNA-Sseq. We randomly split 60 samples into two groups: training set (20 cancer, 20 normal) and , testing set (10 cancer, 10 normal). We apply 10-fold cross-validation to determine hyperparameter of five machine learning models and use the ensemble learning method to evaluate the predictive value of the small RNAs in the exosome by integrating the five machine learning models. Results: The ensemble learning model achieved the testing accuracy of 85% with the sensitivity of 70% and the specificity of 100% by using small RNA and CA125 abundance level as input features. While uUsing CA125 alone, the testing accuracy equals to 90% with the sensitivity of 80% and the specificity of 100%. For the 11 eleven early-stage patient samples, our ensemble learning model made 2 false negative predictions with a total accuracy of 95.1% (sensitivity=81.8%, specificity=100%) while using CA125 alone had five 5 false negative predictions with a total accuracy of 87.8% (sensitivity=54.5%, specificity=100%). All 30 control samples had been correctly classified. Conclusions: We found that ensemble learning model using combining both exosome small RNAs and CA125 will not improve the prediction accuracy for late-stage cancer patients compared to CA125 alone but will significantly improve the prediction accuracy for early-stage patients. Our research findings may indicate a two-pronged strategy in assessing ovarian cancer risks using existing CA125 test followed by small RNA features to detect early-stage ovarian cancer. We are now collecting a larger number of early-stage cancer patient samples for validation. Citation Format: Yuliang Cao, Cun Han, Jianting Sheng, Samuel Mok, Stephen T.C. Wong. Exosomal non-coding RNAs as a biomarker to improve early ovarian cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3333.

Pathways to diagnosis of endometrial and ovarian cancer in the 45 and Up Study cohort

PurposeTo determine pathways to endometrial or ovarian cancer diagnosis by comparing health service utilization between cancer cases and matched cancer-free controls, using linked health records.MethodsFrom cancer registry records, we identified 238 incident endometrial and 167 ovarian cancer cases diagnosed during 2006–2013 in the Australian 45 and Up Study cohort (142,973 female participants). Each case was matched to four cancer-free controls on birthdate, sex, place of residence, smoking status, and body mass index. The use of relevant health services during the 13–18-, 7–12-, 0–6-, and 0–1-months pre-diagnosis for cases and the corresponding dates for their matched controls was determined through linkage with subsidized medical services and hospital records.ResultsHealthcare utilization diverged between women with cancer and controls in the 0–6-months, particularly 0–1 months, pre-diagnosis. In the 0–1 months, 74.8% of endometrial and 50.3% of ovarian cases visited a gynecologist/gynecological oncologist, 11.3% and 59.3% had a CA125 test, 5.5% and 48.5% an abdominal pelvic CT scan, and 34.5% and 30.5% a transvaginal pelvic ultrasound, respectively (versus ≤ 1% of matched controls). Moreover, 25.1% of ovarian cancer cases visited an emergency department in the 0–1-months pre-diagnosis (versus 1.3% of matched controls), and GP visits were significantly more common for cases than controls in this period.ConclusionMost women with endometrial or ovarian cancer accessed recommended specialists and tests in the 0–1-months pre-diagnosis, but a high proportion of women with ovarian cancer visited an emergency department. This reinforces the importance of timely specialist referral.

Methylated Septin9 has moderate diagnostic value in colorectal cancer detection in Chinese population: a multicenter study

BackgroundThe detection rate of methylated Septin9 (mSEPT9) in colorectal cancer (CRC) is varied greatly across the studies. This study aimed to evaluate the diagnostic ability of mSEPT9 in CRC, and compare the diagnostic efficacy with fecal immunochemical test (FIT).Methods326 subjects from four centers were prospectively recruited, including 179 CRC and 147 non-CRC subjects. The plasma was collected for mSEPT9 and CEA, AFP, CA125, CA153 and CA199 test, and fecal samples for FIT tests. Sensitivity, specificity and area under the curve (AUC) of receiver operating characteristic curve were calculated to evaluate the diagnostic value of each biomarker.ResultsThe positive rate in mSEPT9 and FIT, and the level of CEA, CA125 and CA199 were significantly higher in CRC compared with non-CRC subjects. The mSEPT9 positive rate was not associated with TNM stage and tumor stage. The sensitivity, specificity and AUC of mSEPT9 in diagnostic CRC were 0.77, 0.88 and 0.82, respectively, while the value in FIT was 0.88, 0.80 and 0.83, respectively. mSEPT9 and FIT have higher AUC value than that of CEA, CA125 and CA199. Combination of both mSEPT9 and FIT positive increased sensitivity and AUC to 0.98 and 0.83, respectively, but the specificity was declined. mSEPT9 has a slightly low sensitivity in diagnosis of colon cancer (0.87) compared with rectal cancer (0.93).ConclusionmSEPT9 demonstrated moderate diagnostic value in CRC detection, which was similar to the FIT but superior to the CEA, CA125 and CA199. Combination of mSEPT9 and FIT further improved diagnostic sensitivity in CRC.Trial registration: ChiCTR2000038319.

Serum CA-125 for the diagnosis of pulmonary tuberculosis: a systematic review and meta-analysis

BackgroundPulmonary tuberculosis (PTB) remains the world’s deadliest infectious killer. Serum CA-125 test are useful in the diagnosis of PTB. Although studies on the relation between CA-125 and PTB have been reported, the specificity and sensitivity of serum CA-125 in diagnosing PTB vary widely among different studies. The present study was performed to evaluate the accuracy of CA-125 for the diagnosis of PTB via a meta-analysis of data obtained from previous studies.MethodsEnglish and Chinese medical electronic databases were searched for eligible studies published up to February 2020. STATA software was used to obtain a pooled estimation of the diagnostic accuracy of CA-125 and analyze the heterogeneity of the recruited studies. Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to evaluate the quality of the obtained studies.ResultsA total of 16 articles were included in this study. The pooled sensitivity and specificity of CA-125 were 0.85 [95% confidence interval (CI) 0.75–0.91] and 0.87 (95% CI 0.78–0.93), respectively. Moreover, the pooled positive likelihood ratio (LR+), negative likelihood ratio (LR−), and diagnostic odds ratio (DOR) of CA-125 were 6.65 (95% CI 3.62–12.20), 0.18 (95% CI 0.10–0.31), and 37.82 (95% CI 13.17–108.60), respectively. The area under the summary receiver operating characteristic curve (AUC) was 0.93.ConclusionsTaken together, the results indicate that serum CA-125 presents potential practical value for diagnosing PTB, but its clinical applicability must be further examined.

Evaluating Specivity, Sensitivity, Positive and Negative Predictive Values of CA125 for Diagnosing Ovarian Cancer

Background and Aim: Ovarian cancer is among the most common cancers in women worldwide. CA125 is the most frequent biomarker used in the screening for ovarian cancer. CA125 has no high sensitivity and specificity as a screening test in the medical community; however, because of being simple and noninvasive, it is almost always requested for evaluation and ruling out cancer. It plays an important role in the treatment and post-treatment process, the prediction of prognosis, and the relapse of the disease. The present study aimed to determine the relationship between a high level of CA125 tumor marker and ovarian cancer by detecting spesivity, sensivity, positive and negative predictive values. Methods & Materials: In this cross-sectional study, all cases undergoing CA125 test in Velayat Hospital in 2017-1028 were evaluated for having ovarian cancer. In addition, the CA125 level was compared between healthy individuals and patients with ovarian cancer. Finally, the obtained data were analyzed using SPSS. Ethical Considerations: The present study was approved by the Qazvin University of Medical Sciences (Ethics Code: IR.QUMS.REC.1396.316). Results: In this study, 35.3% of the study participants received a definite diagnosis of ovarian cancer. Generally, CA125 values were negative in 41.8% and positive in.58.2% of the study subjects. The sensitivity of the test was measured as 80.1%, the specivity as 53.6%, the positive predictive value equaled 48.4%, and the negative predictive value was measured as 83%. There was a significant relationship between age and the presence of ovarian cancer, and serum CA125 levels. Conclusion: The present study suggested that age and the serum level of CA125 were statistically significant. Finally, CA125 levels were significantly related to ovarian cancer. It provided moderate specivity and specivity as well as low positive predictive value and high negative predictive value as a tumor marker; it is valuable for ruling out of tumor but not appropriate as a screening test.

Machine learning-based LIBS spectrum analysis of human blood plasma allows ovarian cancer diagnosis.

Early-stage screening and diagnosis of ovarian cancer represent an urgent need in medicine. Usual ultrasound imaging and cancer antigen CA-125 test when prescribed to a suspicious population still require reconfirmations. Spectroscopic analyses of blood, at the molecular and atomic levels, provide useful supplementary tests when coupled with effective information extraction methods. Laser-induced breakdown spectroscopy (LIBS) was employed in this work to record the elemental fingerprint of human blood plasma. A machine learning data treatment process was developed combining feature selection and regression with a back-propagation neural network, resulting in classification models for cancer detection among 176 blood plasma samples collected from patients, including also ovarian cyst and normal cases. Cancer diagnosis sensitivity and specificity of respectively 71.4% and 86.5% were obtained for randomly selected validation samples.

Impact of Genetic Testing on Risk-Management Behavior of Black Breast Cancer Survivors: A Longitudinal, Observational Study.

Black women are overrepresented among premenopausal breast cancer (BC) survivors. These patients warrant genetic testing (GT) followed by risk-reducing behaviors. This study documented patterns and predictors of cancer risk-management behaviors among young black BC survivors after GT. Black women (n = 143) with a diagnosis of BC at the age of 50years or younger received GT. At 1year after GT, participants reported receipt of risk-reducing mastectomy, risk-reducing salpingo-oophorectomy, mammogram, breast magnetic resonance imaging (MRI), CA125 test, and transvaginal/pelvic ultrasound. Logistic regression was used to examine predictors of BC risk management (risk-reducing mastectomy or breast MRI) and ovarian cancer risk management (risk-reducing salpingo-oophorectomy, CA125 test, or transvaginal/pelvic ultrasound). Of the study participants, 16 (11%) were BRCA1/2-positive, 43 (30%) had a variant of uncertain significance, and 84 (59%) were negative. During the 12months after GT, no women received risk-reducing mastectomy. The majority (93%) received a mammogram, and a smaller proportion received breast MRI (33%), risk-reducing salpingo-oophorectomy (10%), CA125 test (11%), or transvaginal/pelvic ultrasound (34%). Longer time since the BC diagnosis predicted lower likelihood of BC risk management (odds ratio [OR] 0.54). BRCA1/2 carrierstatus (OR 4.57), greater perceived risk of recurrence (OR 8.03), and more hereditary breast and ovarian cancer knowledge (OR 1.37) predicted greater likelihood of ovarian cancer risk management. Young black BC survivors appropriately received mammograms and ovarian cancer risk management based on their BRCA1/2 test result. However, the low usage of MRI among BRCA1/2 carriers contrasts with national guidelines. Future research should examine barriers to MRI among black BC survivors. Finally, modifiable variables predicting risk management after GT were identified, providing implications for future interventions.

CA125 over-release behavior following a 75-g oral glucose test as a predictive biomarker of multidrug resistance in patients with ovarian cancer.

Multidrug resistance is a major cause of death in patients with ovarian cancer. To improve patient survival, we developed a novel, noninvasive and convenient tool, the 75-gram oral glucose (75gOG)-stimulated CA125 test, to monitor cancer chemoresistance in real time. Our in vitro proof-of-principal experiments revealed that post-75gOG glucose and insulin peaks can synergistically increase cancer-derived CA125 levels, and the increase in CA125 secretion (ΔCA125) is correlated with the overactivation of the insulin receptor (IR)-PI3K-Akt axis and increases (ΔIC50 s) in cisplatin/taxol IC50 s. Correspondingly, among the 93 patients enrolled, post-75gOG CA125 over-release (i.e., enhanced ΔCA125) behavior was associated with overexpression of the IR-PI3K-Akt pathway and its downstream components, namely, IR, pAkt, pS6 and GLUT4, in cancer specimens. Furthermore, both pre- and postsurgical 75gOG CA125 tests demonstrated that CA125 over-release showed excellent prediction efficacy on the chemoresistance potential of ovarian cancer; notably, the former indicated the need for an optimal debulking surgery, and the latter suggested the use of IR-PI3K-Akt inhibitors. Both test results possess independent prognostic significance for the 2-year progression-free survival (PFS) and overall survival (OS) of patients. The odds ratios and corresponding 95% confidence intervals (95% CIs) were 2.680 (95% CI: 1.393-5.156) for patients with CA125 over-release behavior evidenced by a presurgical 75gOG CA125 test or 3.822 (95% CI: 1.942-7.522) for that evidenced by a postsurgical test in PFS; and 3.320 (95% CI: 1.508-7.309) for patients with CA125 over-release behavior evidenced by a presurgical test or 5.212 (95% CI: 2.241-12.121) for that evidenced by a postsurgical test in OS.

The accuracy of preoperative serum CA-125 levels to predict lymph node metastasis in a population of South African women with endometrial carcinoma

Background: The purpose of the study was to evaluate the predictive value of serum CA-125 levels in the preoperative assessment of endometrial carcinoma in a setting where late presentation is common.Method: This retrospective study evaluated women with pathologically proven endometrial carcinoma scheduled for surgery between January 2012 and January 2017, who had preoperative serum CA-125 test results. The association of CA-125 with a variety of histological factors was evaluated using Spearman’s correlation and receiver operator characteristic (ROC) curves to evaluate sensitivity and specificity.Results: Fifty-eight patients were included in the study, 34 (58.6%) of whom were FIGO stage II–IV. Elevated CA-125 levels were significantly correlated with late FIGO stage (p < 0.001), myometrial invasion (p < 0.001) and lymph node metastases (p < 0.001). The most appropriate cut-off point of CA-125, where an increase in sensitivity was not associated with a fall-off in specificity, was 20 IU/ml, reaching a sensitivity of 90% and a specificity of 67% for detection of lymph node metastases.Conclusion: Among this group of women with endometrial cancer, the preoperative serum CA-125 level was associated with lymph node metastases and we found a CA-125 of 20 IU/ml or more to be predictive. These findings suggest that, among similar populations, CA-125 could be done preoperatively and could be used to determine the need for node dissection. Since our findings are from a small retrospective cohort, this should be validated in a prospective study on early stage disease.

SERS-based detection of haptoglobin in ovarian cyst fluid as a point-of-care diagnostic assay for epithelial ovarian cancer.

PurposeTo evaluate haptoglobin (Hp) in ovarian cyst fluid as a diagnostic biomarker for epithelial ovarian cancers (EOCs) using surface-enhanced Raman spectroscopy (SERS)-based in vitro diagnostic assay for use in an intraoperative setting.MethodsSERS-based method was used to detect and quantify Hp in archived ovarian cyst fluids collected from suspicious ovarian cysts and differentiate benign tumors from EOCs. The diagnostic performance of SERS-based assay was verified against the histopathology conclusions and compared with the results of CA125 test and frozen sections.ResultsHp concentration present in the clinical cyst fluid measured by SERS was normalized to 3.3 mg/mL of standard Hp. Normalized mean values for patients with benign cysts were 0.65 (n=57) and malignant cysts were 1.85 (n=54), demonstrating a significantly (P<0.01) higher Hp in malignant samples. Verified against histology, Hp measurements using SERS had a sensitivity of 94% and specificity of 91%. Receiver operating characteristic curve analysis of SERS-based Hp measurements resulted in area under the curve of 0.966±0.03, establishing the robustness of the method. CA125 test on the same set of patients had a sensitivity of 85% and specificity of 90%, while frozen section analysis on 65 samples had 100% sensitivity and specificity.ConclusionWith a total execution time of <10 minutes and consistent performance across different stages of cancer, the SERS-based Hp detection assay can serve as a promising intra-operative EOC diagnostic test.

Comparison of Longitudinal CA125 Algorithms as a First-Line Screen for Ovarian Cancer in the General Population.

Purpose: In the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), women in the multimodal (MMS) arm had a serum CA125 test (first-line), with those at increased risk, having repeat CA125/ultrasound (second-line test). CA125 was interpreted using the "Risk of Ovarian Cancer Algorithm" (ROCA). We report on performance of other serial algorithms and a single CA125 threshold as a first-line screen in the UKCTOCS dataset.Experimental Design: 50,083 post-menopausal women who attended 346,806 MMS screens were randomly split into training and validation sets, following stratification into cases (ovarian/tubal/peritoneal cancers) and controls. The two longitudinal algorithms, a new serial algorithm, method of mean trends (MMT) and the parametric empirical Bayes (PEB) were trained in the training set and tested in the blinded validation set and the performance characteristics, including that of a single CA125 threshold, were compared.Results: The area under receiver operator curve (AUC) was significantly higher (P = 0.01) for MMT (0.921) compared with CA125 single threshold (0.884). At a specificity of 89.5%, sensitivities for MMT [86.5%; 95% confidence interval (CI), 78.4-91.9] and PEB (88.5%; 95% CI, 80.6-93.4) were similar to that reported for ROCA (sensitivity 87.1%; specificity 87.6%; AUC 0.915) and significantly higher than the single CA125 threshold (73.1%; 95% CI, 63.6-80.8).Conclusions: These findings from the largest available serial CA125 dataset in the general population provide definitive evidence that longitudinal algorithms are significantly superior to simple cutoff values for ovarian cancer screening. Use of these newer algorithms requires incorporation into a multimodal strategy. The results highlight the importance of incorporating serial change in biomarker levels in cancer screening/early detection strategies. Clin Cancer Res; 24(19); 4726-33. ©2018 AACR.

Postprandial increase in serum CA125 as a surrogate biomarker for early diagnosis of ovarian cancer

BackgroundCA125 is a prevalently used serum biomarker for detecting ovarian cancer over the last three decades. However, it has a significant deficiency in screening for early-stage cancer. With the purpose of exploring an effective approach to improve its performance in early diagnosis, we investigated the postprandial fluctuation pattern of cancer-derived CA125 and the underlying mechanism.MethodsIn two medical centers, 551 patients sonographically diagnosed with ovarian (adnexal) cysts (< 5 cm in diameter) were enrolled and divided into five disease groups (pelvic inflammatory cysts, retention cysts, endometrioma, benign/borderline cystadenoma and malignant cysts). The subtle differences in 1-h postprandial serum CA125 increases were compared between disease groups. A support vector machine (SVM)-based algorithm was used for refining the performance of CA125 postprandial increment. Ovarian cancer xenograft animal and cancer cell models were used to recapitulate the clinical findings and reveal the molecular basis of postprandial blood glucose and insulin in invoking the synthesis/secretion/re-absorption of CA125.ResultsPatients with ovarian cancer presented the highest postprandial increment 13.3 ± 0.7% (mean ± standard deviation) among the five disease groups. Using a CA125 increment ≥ 10% criterion, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) reached 83.3, 96.3, 61.1 and 98.8%, respectively, for early-stage ovarian cancer. This performance was further improved by the SVM-based CA125-increment algorithm, which exhibited 91.7% sensitivity, 99.2% specificity, 89.2% PPV and 99.4% NPV. Both modalities manifested diagnostic advantages over the traditional CA125 test (75.0% sensitivity, 25.4% specificity, 6.6% PPV and 93.6% NPV at the cut-off of 35 U/mL). Regarding the molecular basis, the postprandial blood glucose and insulin-invoked overexpression of Mucin 16 (encoding CA125) were demonstrated in animal and cancer cell models, which were mediated by the PI3K-Akt pathway. Nevertheless, a Mesothelin-based CA125 re-absorption behavior was noted in the treated cancer cells, which contributed to the over-drop following the postprandial peak of serum CA125.ConclusionsCancer-derived serum CA125 possesses a unique and distinctive postprandial pattern, that distinguishes it from the common CA125 elevation in a benign disease condition. The dynamic measurement/assessment strategy can achieve a discriminatory power superior to that of a static test.

Serum CA125 in combination with ferritin improves diagnostic accuracy for epithelial ovarian cancer

Introduction: CA125 has poor sensitivity and low specificity for detecting early ovarian cancer. Serum ferritin is elevated in many malignancies. We evaluated the performance of ferritin alone and in combination with CA125 as a diagnostic tool to detect epithelial ovarian cancer (EOC).Methods: CA125 and ferritin were detected in the serum of 50 healthy control (HC), 50 women with benign gynaecological conditions and 124 women with EOC. The relationship between serum ferritin and CA125 and each of the clinicopathological parameters was assessed, and their diagnostic accuracy for discriminating ovarian cancer determined.Results: Serum ferritin and CA125 were higher in patients with EOC compared to HCs and patients with benign conditions (both p < 0.001). There was no relationship between levels of ferritin and CA125. Both ferritin and CA125 discriminated HC from EOC (p < 0.05), but ferritin showed better diagnostic accuracy than CA125 (p = 0.048). Ferritin was superior to CA125 in discrimination early EOC (p = 0.002), but in advanced stages, CA125 was superior (p = 0.026). A combination of ferritin and CA125 marginally increases the diagnostic accuracy to discriminate EOC from HCs.Conclusion: Ferritin discriminates between HCs and EOC patients, especially in early stage disease. The combination of serum ferritin and CA125 provides the higher diagnostic accuracy to screen for EOC. Serum ferritin could serve as an EOC biomarker to complement the standard CA125 test.

Evaluation of Circulating Endometrial Cells as a Biomarker for Endometriosis.

Background:Circulating endometrial cells (CECs) have been reported to be present in the peripheral blood of women with endometriosis (EM), providing clear and specific evidence of the presence of ectopic lesions. In this study, we established a method with a high detection rate of CECs, assessed the diagnostic value of CECs for EM and compared with serum CA125, and proposed a hypothesis for the pathogenesis of EM from the new perspective of CECs.Methods:The participants were enrolled prospectively from October 2015 to July 2016. The peripheral blood samples were collected from 59 participants, and the blood cells were isolated for immunofluorescence staining via microfluidic chips. The cells that were positive for vimentin/cytokeratin and estrogen/progesterone receptor and negative for CD45 were identified as CECs. The serum CA125 level was tested with electrochemiluminescence immunoassay.Results:The detection rate of CECs reached 89.5% (17/19) in the EM group, which was significantly higher than that of the control group (15.0% [6/40], P < 0.001) and was independent of menstrual cycle phases. Furthermore, a positive CEC assay detected 4/5 cases of Stage I–II EM. In contrast, a positive CA125 test had limited value in detecting EM (13/19, 68.4%) and detected only one case of Stage I–II EM.Conclusion:CECs are promising biomarkers for EM with great potential for a noninvasive diagnostic assay.

The First Nationwide Multicenter Prevalence Study of Germline BRCA1 and BRCA2 Mutations in Chinese Ovarian Cancer Patients.

Subjects with germline BRCA1/2 mutations (gBRCAm) have an increased risk of developing ovarian cancer and enhanced sensitivity to platinum-containing agents and PARP (poly[ADP-ribose] polymerase) inhibitors. BRCA mutations in Asian patients are poorly understood compared with other populations. We aimed to investigate gBRCAm prevalence and characteristics in Chinese ovarian cancer patients. We conducted the first nationwide multicenter gBRCAm prevalence study in China. Eight hundred twenty-six unselected ovarian cancer patients from 5 clinical centers were enrolled and tested for gBRCAm status. Medical data including age, family history, previous treatments, clinical diagnosis, histopathologic diagnosis, tumor grade, platinum sensitivity, and CA-125 test result were reviewed and collected. Prevalence rate or gBRCAm was determined as 28.5%, with 20.8% of patients harboring BRCA1 mutation and 7.6% harboring BRCA2 mutation. The group had a higher percentage of high-grade serous (73.0%), late-stage (III and IV [85.5%]) patients and a younger median age at diagnosis (52 years) compared with other reported studies. Twnety-seven BRCA1 and 17 BRCA2 mutations have not been reported previously in public databases or the literature. Statistically significant correlations were observed between gBRCAm status and family history (P < 0.001), gBRCAm status, and tumor stage (P = 0.02). A numerical higher prevalence of gBRCAm in patients with high-grade serous histopathology (30.9%), platinum-sensitive phenotype (34%), and late-line chemotherapy was observed. Germline BRCA1/2 mutations is common in Chinese ovarian cancer patients. This study implies that all ovarian patients should be tested for gBRCAm status regardless of family history and histopathology.

Prognostic analysis of invasive circulating tumor cells (iCTCs) in epithelial ovarian cancer

GoalsCirculating tumor cells (CTCs) have been introduced as a biomarker in detecting advanced epithelial ovarian cancer (EOC). The goals are to examine the prevalence of the invasive subpopulation of CTCs (iCTCs) in patients at high risk of EOC and to compare this biomarker to serum CA125. MethodsWe used a unique cell adhesion matrix (CAM)-based, functional cell enrichment and identification platform to isolate iCTCs from 129 preoperative patients. We confirmed the identity of iCTCs using positive epithelial (Epi+) markers and negative hematopoietic lineage (HL−) markers. Sensitivity and specificity of the assays were examined and iCTCs/CA125 were correlated with overall survival (OS), progression-free survival (PFS) and clinical parameters. ResultsWe found a 41.2% sensitivity, 95.1% specificity and 77.8% positive predictive value (PPV) of the iCTC assay in detecting patients with stage I and II EOC malignancy, and a 83% sensitivity and 97.3% PPV in detecting all stages of EOC malignancy. However, a positive CA125 test provided weak evidence to detect stage I and II malignancy (61.6% PPV) and all EOC (92.1% PPV), because of its 76.2% specificity. A significantly stronger concordance in OS and PFS of clinical factors (tumor stage, debulking and platinum sensitivity) was noted for elevated iCTCs than for serum CA125. ConclusionThe CAM-initiated CTC enrichment/identification method enabled the detection of early stage EOC. iCTCs were better correlated with worse OS and PFS, more specific and better PPV than CA125 in detecting EOC malignancy in patients at high risk of EOC.

Methods for Identifying the Cost-effective Case Definition Cut-Off for Sequential Monitoring Tests: An Extension of Phelps and Mushlin

The arrival of personalized medicine in the clinic means that treatment decisions will increasingly rely on test results. The challenge of limited healthcare resources means that the dissemination of these technologies will be dependent on their value in relation to their cost, i.e., their cost effectiveness. Phelps and Mushlin have described how to optimize tests to meet a cost-effectiveness target. However, when tests are applied repeatedly the case mix of the patients tested changes with each administration, and this impacts upon the value of each subsequent test administration. In this article, we present a modification of Phelps and Mushlin's framework for diagnostic tests; to identify the cost-effective cut-off for monitoring tests. Using the Ca125 test monitoring for relapse in ovarian cancer, we show how the repeated use of the initial cut-off can lead to a substantially increased false-negative rate compared with the monitoring cut-off-over 4% higher than in this example-with the associated harms for individual and population health.