A disposable ultrasensitive immunosensor based on MXene/NH2-CNT modified screen-printed electrode for the detection of ovarian cancer antigen CA125.

Cancer antigen 125 (CA125) is the gold standard biomarker for clinical diagnosis of ovarian cancer, with a threshold value of 35 U/mL in serum. In this paper, a disposable ultrasensitive immunosensor based on Ti3C2Tx-MXene/amino-functionalized carbon nanotube (NH2-CNT) modified screen-printed carbon electrode (SPCE) was constructed for the detection of the ovarian cancer antigen CA125. By optimizing the mass ratio of Ti3C2Tx to NH2-CNT, Ti3C2Tx/NH2-CNT composite with excellent electrochemical properties was prepared, which is beneficial for amplifying the initial electrochemical signal. The positively charged NH2-CNT effectively alleviated the stacking problem of Ti3C2Tx, and its amino group also facilitated the covalent immobilization of the capture antibody. Meanwhile, chitosan (CS) with excellent film-forming ability was also used to successfully enhance the adsorption of electrode material, thus improving the stability of the sensor. In addition, CS could further enhance the current signal. The prepared immunosensor exhibited excellent performance in CA125 detection with a wide linear range from 1 mU/mL to 500 U/mL, and good selectivity, reproducibility and lomg-term stability. Furthermore, the immunosensor showed satisfactory results for the detection of CA125 in clinical serum samples, which is promising for the clinical screening, early diagnosis and prognostic examination of ovarian cancer.

Automated early ovarian cancer detection system based on bioinformatics.

Ovarian cancer is a common gynecological tumor, with a high mortality rate and difficult clinical treatment. Early detection of ovarian cancer has significant diagnostic value. In response to the problem of poor diagnostic performance of traditional early diagnosis methods, this article designed an automated early ovarian cancer detection system to improve the detection of early ovarian cancer. The conventional early diagnosis methods include serum CA125 (carbohydrate antigen 125) detection and positron emission tomography/computed tomography (PET/CT) imaging. This article combined serum CA125 detection and PET/CT imaging to detect the CA125 level and maximum standardized uptake value (SUV) in patient's serum. When the CA125 level exceeded 35U/ml and the maximum SUV value exceeded 2.5, the test was considered positive. This article selected 200 patients from Jingzhou Hospital for the experiment and compared the three detection methods. The average specificity of single serum CA125 detection, single PET/CT imaging, and automated detection in patients under 50 were 61.24%, 79.57%, and 97.79%, respectively. The automated early ovarian cancer detection system designed in this article can significantly improve the specificity of early ovarian cancer detection and has excellent application value for early ovarian cancer detection.

Risk-stratified CA125 screening integrating CA125 trajectories, trajectory-specific progression and transvaginal ultrasound for ovarian cancer.

BACKGROUNDS: Cancer antigen 125 (CA125) is widely used for screening ovarian cancer (OC), yet its effectiveness remains debated. Potential factors may include ineffective cut-off value for CA125 in screening, as well as a lack of consideration for CA125 trajectories and trajectory-specific progression. METHODS: Based on data from multiple rounds of CA125 tests and transvaginal ultrasound (TVU) examinations conducted on 28,456 women in the PLCO Trial, time-dependent receiver-operating-characteristic curves (ROCs) and area-under-the-curves (tdAUCs) analyses were employed to identify the optimal CA125 cut-off values for OC screening. Participants were categorized into four CA125 trajectories: stable negative CA125 (CA125SN), loss of positive CA125 (CA125LP), stable positive CA125 (CA125SP), and gain of positive CA125 (CA125GP). The associations between different CA125 trajectories, trajectory-specific progression indicators, and OC risk were explored. The effectiveness of risk-stratified CA125 screening, incorporating CA125 trajectories, trajectory-specific progression, and TVU, was evaluated using hazard ratio and 95% confidence intervals [HR (95%CIs)], with adjustments for potential confounders. RESULTS: After a median follow-up of 14.8 years for OC incidence and 23.8 years for OC mortality, 250 OC cases and 218 OC deaths were identified. The tdAUC for 10-year OC incidence with CA125 was 0.663, with an optimal cut-off value of 13.00 U/ml. Trajectory analyses showed that both CA125SP and CA125GP were significantly associated with increased risks of OC incidence [HRs (95%CIs): 2.00(1.47-2.73) and 3.06(2.25-4.16)] and mortality [HRs (95%CIs):1.58(1.13-2.21) and 2.60(1.87-3.62)] compared to CA125SN. Trajectory-specific progression analyses identified relative velocity as the optimal progression indicators for both CA125SP and CA125GP (tdAUCs: 0.712 and 0.767), with optimal cut-off values of 9% and 32% per year, respectively. Positive progression was associated with significantly increased risks of OC incidence [HRs (95%CI): 7.26(4.00-13.17) and 3.83(1.96-7.51) CA125GP and CA125SP] and mortality [HRs (95%CI): 8.03(4.15-15.56) and 6.04(2.78-13.14)] compared to negative progression. Optimized risk-stratified CA125 screening, which integrated CA125 trajectories, trajectory-specific progression, and TVU, reduced missed OC by 3.6% and improved accuracy compared to traditional screening methods. CONCLUSIONS: Incorporating CA125 trajectories and trajectory-specific progression into screening protocols enhances the identification of the population at high-risk of OC. An optimized screening strategy, which includes these factors along with TVU, is recommended to improve the effectiveness of OC screening.

MUC16/CA125 in cancer: new advances.

MUC16/CA125 is a common diagnostic marker for many types of cancer. However, due to the widespread expression of MUC16 in cancer, its specificity and sensitivity as a target are poor, which severely limits its clinical application. In recent years, various studies have shown that the clinical application potential of MUC16/CA125 has been greatly improved. The update of detection technology improves the accuracy and range of detection, and improves the early diagnosis rate of cancer. Targeting MUC16/CA125 is an important strategy for tumor therapy. Targeting residual amino acids, n-glycoylation structures or other targets on the surface of MUC16 cells can greatly improve the accuracy of detection and therapy. The new drug delivery method broke through the original technical shackles, targeted MUC16 positive cells more specifically and improved the drug efficacy. In this paper, the technological advances in detecting and identifying MUC16 targets and the great progress in cancer screening and treatment based on MUC16 as a target are described in detail, revealing the great potential of MUC16 as a target in cancer screening and treatment, and illustrating the potential clinical application value of MUC16.

Evaluating pretreatment serum CA-125 levels as prognostic biomarkers in endometrial cancer: a comprehensive meta-analysis.

Background: In recent years, the incidence of endometrial cancer (EC) has been rising. This meta-analysis aims to clarify the prognostic significance of serum CA-125 levels in EC. Methods: Articles up to March 1, 2024, were systematically searched in EMBASE, Cochrane Library, PubMed, and Web of Science. This analysis pooled hazard ratios (HR) and 95% confidence intervals (CI) from qualifying studies to evaluate the association of CA-125 levels with overall survival (OS), progression-free survival (PFS), disease-free/relapse-free survival (DFS/RFS), and disease-specific survival (DSS). Results: 25 studies involving 7,716 patients were included. The analysis revealed that elevated CA-125 levels correlate with poorer OS (HR = 1.848, 95% CI: 1.571-2.175, p < 0.001). This association persisted across various study regions and sample sizes, and was notably strong in subgroups with a CA-125 cut-off value of less than 35 (HR = 2.07, 95% CI: 1.13-3.80, p = 0.019) and equal to 35 (HR = 2.04, 95% CI: 1.49-2.79, p < 0.001), and among type II pathology patients (HR = 1.72, 95% CI: 1.07-2.77, p = 0.025). Similarly, high CA-125 levels were linked to reduced PFS, particularly in subgroups with a CA-125 cut-off value less than 35 (HR = 1.87, 95% CI: 1.15-3.04, p = 0.012) and equal to 35 (HR = 4.94, 95% CI: 2.56-9.54, p < 0.001), and in endometrioid endometrial cancer patients (HR = 2.28, 95% CI: 1.18-4.40, p = 0.014). Elevated CA-125 levels were also indicative of worse DFS/RFS (HR = 2.17, 95% CI: 1.444-3.262, p < 0.001) and DSS (HR = 2.854; 95% CI: 1.970-4.133, p < 0.001). Conclusion: Serum CA-125 levels before treatment was highly associated with prognosis of EC patients.

Prognostic Significance of Tumor and Inflammatory Markers in Disease-Free and Overall Survival Duration in Colonic Adenocarcinoma Patients.

Introduction Colorectal carcinoma (CRC) continues to be a major global health concern, contributing substantially to cancer incidence and mortality. Colonic adenocarcinoma, a common subtype of CRC, is influenced by various prognostic factors, including tumor stage, histopathological characteristics, and tumor markers. Despite their routine use in clinical settings, the prognostic value of traditional tumor markers, such as carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), and others, is still under debate. In this study, we aim to analyze the tumor markers' prognostic significance in our CRC patients in terms of disease-free survival and overall survival. Methods A retrospective study was conducted on 71 patients who underwent surgery for colonic adenocarcinoma between January 1, 2018, and January 1, 2024. Data on patient demographics, recurrence rates, survival times, and tumor marker levels (CEA, CA 19-9, CA 125, AFP, and CRP to albumin ratio (CAR)), disease-free survival duration (DFS), and overall survival durations (OS) were collected and analyzed. Statistical analyses included Pearson and Spearman correlation coefficients, the Mann-Whitney U test, ROC curve analysis, and Kaplan-Meier survival analysis. Results The study found that elevated CAR and CA 125 levels were significantly associated with higher mortality and recurrence rates, whereas elevated CEA levels were strongly predictive of recurrence. Receiver operating characteristic (ROC) analysis identified optimal cutoff values for these markers, with CEA ≥ 47.145, CA 125 ≥ 15.85, and CAR ≥ 6.796 demonstrating high specificity and predictive value for recurrence. Kaplan-Meier analysis revealed that patients with CEA < 47.145 had a significantly longer DFS (67.7 months) compared to those with CEA ≥ 47.145 (24 months, p < 0.001). Similarly, patients with CA 125 < 15.85 and CAR < 6.796 showed longer DFS compared to those with higher values. Overall survival analysis also highlighted that patients with CA 125 < 21.71 and CAR < 4.09 had better survival outcomes, with significant differences of 26 and 10 months, respectively (p < 0.001 and p = 0.001). Conclusion Tumor markers, such as CEA, CA 125, and CAR, hold significant prognostic value in colonic adenocarcinoma, with higher levels correlating with poorer outcomes. These findings underscore the importance of integrating tumor markers into clinical decision-making to optimize treatment strategies and improve patient survival. Future research should focus on standardizing the use of these markers and exploring novel biomarkers for enhanced prognostication.

A rare case of peritoneal tuberculosis mimicking peritoneal carcinomatosis: the ongoing challenge.

Tuberculosis (TB) is a serious infection that can involve any organ system and present in various forms. About one-third of the world's population are carriers of latent TB. Although most cases are from a pulmonary origin, there is a rising prevalence of abdominal TB. Patients with pulmonary or extrapulmonary TB are treated similarly through the use of pharmacological therapy. Nonspecific clinical manifestations of TB have made it difficult for clinicians to diagnose. Peritoneal tuberculosis (PTB) is a serious concern as its symptoms overlap with that of many other chronic conditions, especially in those who are immunocompromised. The lack of highly sensitive and specific testing methods has made early intervention difficult, therefore a high index of suspicion is crucial in the progression of the disease. Here, we present a case of a 71-year-old female with a history of abdominal pain, fever, and weakness. Initial investigation with computed tomography (CT) imaging revealed omental fat stranding that pointed towards peritoneal carcinomatosis (PC) from possible recurrence of her ovarian cancer. Further investigation with a peritoneal biopsy was remarkable for caseating granulomas with fat necrosis confirming extrapulmonary TB. This report highlights a rare case of PTB mimicking PC in an elderly patient who is immunocompromised from the use of long-term corticosteroids who continued to decline after pharmacological treatment of the disease.

Clinical value of ACR O-RADS combined with CA125 in the risk stratification of adnexal masses.

Purpose: To develop a combined diagnostic model integrating the subclassification of the 2022 version of the American College of Radiology (ACR) Ovarian-Adnexal Reporting and Data System (O-RADS) with carbohydrate antigen 125 (CA125) and to validate whether the combined model can offer superior diagnostic efficacy than O-RADS alone in assessing adnexal malignancy risk. Methods: A retrospective analysis was performed on 593 patients with adnexal masses (AMs), and the pathological and clinical data were included. According to the large differences in malignancy risk indices for different image features in O-RADS category 4, the lesions were categorized into groups A and B. A new diagnostic criterion was developed. Lesions identified as category 1, 2, 3, or 4A with a CA125 level below 35 U/ml were classified as benign. Lesions identified as category 4A with a CA125 level more than or equal to 35 U/ml and lesions with a category of 4B and 5 were classified as malignant. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) of O-RADS (v2022), CA125, and the combined model in the diagnosis of AMs were calculated and compared. Results: The sensitivity, specificity, PPV, NPV, accuracy, and AUCs of the combined model were 92.4%, 96.5%, 80.2%, 98.8%, 94.1%, and 0.945, respectively. The specificity, PPV, accuracy, and AUC of the combined model were significantly higher than those of O-RADS alone (all P < 0.01). In addition, both models had acceptable sensitivity and NPV, but there were no significant differences among them (P > 0.05). Conclusion: The combined model integrating O-RADS subclassification with CA125 could improve the specificity and PPV in diagnosing malignant AMs. It could be a valuable tool in the clinical application of risk stratification of AMs.

Generalised Blisters and Respiratory distress: A Case of Bullous Systemic Lupus Erythematosus.

Tjalma's syndrome is a benign combination of ascites, pleural effusion, and elevated CA-125 occurring in patients with systemic lupus erythematosus. Reports of Tjalma's syndrome are scarce. An elevated CA-125 level often suggests the possibility of the presence of a malignant tumor. We report a case of generalised erythema and blisters with pruritus, massive unilateral pleural effusion and elevated CA-125. This patient was finally diagnosed with bullous systemic lupus erythematosus after exclusion of tumour and other maculopapular disorders. We hope that this particular case may provide a more comprehensive and novel diagnostic idea of systemic lupus erythematosus and pleural effusion, avoiding unnecessary anxiety, laboratory tests and surgical interventions.

The application value of two-dimensional ultrasound combined with contrast-enhanced ultrasound in the differential diagnosis of benign, borderline, and malignant ovarian epithelial tumors.

OBJECTIVE: The aim of this study was to explore the clinical application value of two-dimensional ultrasound (2D-US) combined with contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign, borderline ovarian tumors (BOTs), and malignant ovarian epithelial tumors (OETs). METHODS: The clinical data of 108 patients who underwent surgery for pathologically confirmed of OETs at Peking University People's Hospital between December 2018 and November 2023 were retrospectively studied. The diagnostic value of 2D-US combined with CEUS for diagnosing OETs was analyzed using chi-square tests, receiver operating characteristic (ROC) curves, and random forest models. RESULTS: Among the 108 cases of OETs, 23 were benign, 34 were BOTs, and 51 were malignant. Chi-square tests confirmed that the perfusion pattern of the contrast agent plays an important role in the differential diagnosis of OETs. Compared with those in the benign group, the BOTs were not significantly different in terms of perfusion phase and enhancement intensity, but the regression time of the BOTs was earlier (P < 0.05). Compared with the BOTs, the malignant tumors group showed earlier perfusion and higher enhancement intensity, with no significant difference in regression time. The ROC curve results indicated that the combined diagnostic efficiency of 2D-US and CEUS in distinguishing OETs was significantly higher than that of a single diagnostic technique in terms of sensitivity, specificity, accuracy, and AUC. The random forest model results revealed that among the various parameters used in the differential diagnosis of OETs, the perfusion pattern was the most significant factor. CONCLUSION: 2D-US combined with CEUS helps improve the differential diagnostic efficiency for benign, BOTs, and malignant OETs.

Case report: Germline BRCA 2 mutation in primary peritoneal carcinoma: a rare malignancy.

Background: Primary peritoneal carcinoma (PPC) is a rare malignancy. Clinically, its histological morphology resembles that of epithelial ovarian tumors (EOC), often leading to misdiagnosis. Diagnosis and treatment of PPC are time-sensitive because of the rapidly progressive nature of the disease. Case report: Herein, we report the case of a 54-year-old woman who was initially diagnosed with ovarian cancer; however, extensive workup showed evidence of Müllerian PPC origin. Furthermore, the patient harbored a targetable BRCA mutation. Conclusion: The patient was treated with the BRCA-targeting agents and had a good prognosis after surgery.

Heart failure biomarkers and prediction of early left ventricle remodeling after acute coronary syndromes.

INTRODUCTION: Several biomarkers are characteristically elevated in patients with acute heart failure (AHF). Our hypothesis was they could predict early changes in left ventricular (LV) characteristics in acute coronary syndrome (ACS) patients. The objective of this study was two-fold: a) compare circulating concentrations of NT-pro BNP, CA-125, ST2, galectin-3 and pro-adrenomedullin among 4 groups of individuals (healthy controls; patients with ACS without AHF; patients with ACS and AHF and patients admitted for AHF); and b) evaluate whether these biomarkers predict adverse LV remodeling and ejection fraction changes in ACS. METHODS: 6 biomarkers (NT-pro BNP, CA-125, ST2, galectin-3, pro-adrenomedullin and C-reactive) were measured within the first 48 h of admission. Echocardiograms were performed during admission and at 3 months. Variables associated with LV end-diastolic volume (EDV) and ejection fraction (LVEF) change were assessed by multivariate linear regression. RESULTS: We analyzed 51 patients with ACS, 16 with AHF and, 20 healthy controls. NT-pro BNP and ST2 concentrations were elevated at similar values in patients admitted for AHF and ACS complicated with HF but CA-125 concentrations were higher in AHF patients. NT-pro BNP concentrations were positively correlated with CA-125 (rho = 0.58; p < 0.001), ST2 (rho = 0.58; p < 0.001) and galectin-3 (rho = 0.37; p < 0.001) Median change (median days was 83 days after) in EDV and LVEF was 5 %. CA-125 concentrations were positively associated to LV EDV change (ß-coefficient 1.56) and negatively with LVEF trend (ß-coefficient = -0.86). No other biomarker predicted changes in EDV or LVEF. CONCLUSIONS: CA-125 correlates with early LV remodeling and LVEF deterioration in ACS patients.

The portable stochastic sensor as a screening tool for simultaneous determination of HER-1 and CA 125 - a key factor in the rapid recognition of gastric cancer.

The significance of HER-1 and CA 125 lies in their ability to guide cancer diagnosis, treatment, and monitoring, improving personalized care and enhancing prognostic accuracy. The utilization of HER-1 and CA 125 as screening biomarkers for the anticipation of early-stage cancer and monitoring cancer progression is expanding due to the invasive and costly nature of present techniques. In this study, a novel stochastic sensor was developed for the simultaneous determination of HER-1 and CA 125 in whole blood, saliva, and gastric tumor tissue samples using a fast, easy, inexpensive, and portable method. The stochastic sensor was prepared by electropolymerization of cysteine on the surface of the Au-TiO2@rGO/SPCE sensor. The Au-TiO2@rGO nanocomposite was synthesized using a simple chemical reduction process. The proposed sensor showed wide linear concentration ranges and very low limits of quantification (LOQ). The concentration ranges were from 3.9 × 10-14 to 3.9 × 10-8 µg mL-1, with a LOQ of 3.9 × 10-14 µg mL-1 for HER-1. For CA 125, the concentration ranges were from 8.3 × 10-14 to 8.3 × 10-10 U mL-1, with a LOQ of 8.3 × 10-14 U mL-1. Both biomarkers exhibit precise discrimination in different biological samples, with recoveries above 96.78% and RSD values below 0.04%. With a confidence level of 99%, the Student t-test revealed that there is no statistically significant difference between the outcomes obtained by using the poly-Cys/Au-TiO2@rGO/SPCE sensor for screening examinations of biological samples. This was determined because the results were not significantly different from one another.

Elevated carbohydrate antigen 125 (CA125) is associated with incident heart failure and mortality in acute coronary syndrome.

AIMS: Carbohydrate antigen 125 (CA125), a mucin produced by serosal cells in response to mechanical and inflammatory stimuli, has emerged as an important biomarker to guide risk stratification in heart failure (HF). The prognostic value of CA125 in acute coronary syndrome (ACS) patients is less explored. METHODS: In a cohort of 524 ACS patients (73% males, mean age 67 ± 12 years), we assessed the associations between CA125 and the risk for HF and death during a median follow-up period of 27.3 months for incident HF and 39.5 months for mortality. Plasma CA125 was measured within 24 h after admission in the entire cohort and after 6 weeks in a subgroup of 115 elderly patients (>75 years of age). We also assessed the relationships between baseline CA125 and echocardiographic parameters of cardiac structure and function at 1 year post-ACS in this subgroup. RESULTS: Baseline CA125 was associated with incident HF in the entire cohort in a Cox proportional hazards model adjusted for age, sex, cardiovascular (CV) risk factors (diabetes, smoking, hypertension, previous HF, previous ACS and previous stroke), renal function and revascularization {hazard ratio [HR] 1.46 [95% confidence interval (CI) 1.10-1.93] per 1-standard deviation [SD] CA125 increase; P = 0.009}. In the detailed follow-up subgroup, elevated baseline CA125 predicted subsequent deterioration of left ventricular (LV) ejection fraction (LVEF), defined as a >5% absolute LVEF decrease in patients with LVEF ≥ 50% at discharge [odds ratio (OR) 3.31 (95% CI 1.15-9.54) per 1-SD baseline CA125 increase; P = 0.027]. We also found significant correlations between high baseline CA125 and larger LV volumes (LV end-diastolic volume index, Spearman's r = 0.329, P < 0.001; LV end-systolic volume index, r = 0.391, P < 0.001) and left atrial volume index (r = 0.320, P < 0.001) at 1 year post-ACS, indicative of adverse cardiac remodelling. Elevated baseline and follow-up CA125 were associated with increased mortality, independently of age and sex [HR 1.37 (95% CI 1.09-1.71), P = 0.006, per 1-SD baseline CA125; HR 1.98 (95% CI 1.06-3.67), P = 0.031, per increasing 6 week CA125 tertile]. The relationship between 6 week CA125 and incident mortality remained significant in the fully adjusted model [HR 2.23 (95% CI 1.15-4.35) per increasing CA125 tertile; P = 0.018]. CONCLUSIONS: We report independent associations between elevated CA125, LV dysfunction, cardiac remodelling, incident HF and mortality post-ACS. Our results warrant further evaluation of CA125 as a potential biomarker for risk stratification and management of ACS patients, both at the time of the acute coronary event and during follow-up.

The relationship between changes in peritoneal permeability with CA-125 and HIF-1α.

BACKGROUND: Peritoneal fibrosis (PF) is a major, persistent complication of prolonged peritoneal dialysis that eventually leads to peritoneal ultrafiltration failure and termination of peritoneal dialysis. Prolonged exposure to high glucose concentrations, degradation products, uremic toxins, and episodes of peritonitis can cause some changes in the peritoneal membrane, resulting in intraperitoneal inflammation and PF, leading to failure of ultrafiltration and dialysis. CA-125 can be used as a biomarker of peritoneal mesothelial cell count in the peritoneal dialysate and for monitoring cell count in PD patients. Hypoxia-inducible factor 1-alpha (HIF-1α) has been reported to cause PF, but has not been reported to be associated with changes in peritoneal structure. We hypothesized that peritoneal adequacy can be followed using HIF-1α and CA-125 values. In the present study, therefore, we investigated the relationship between HIF-1α and CA-125 levels and parietal membrane permeability changes in PD patients. METHODS: Forty-five patients were included in the study. Peritoneal permeability was constant in 20 of these, while peritoneal permeability increased in 11 and decreased in 14. The HIF-1α value from the blood samples of the patients and the CA-125 measurement from the peritoneal fluids were measured. The relationship between peritoneal variability and CA-125 and HIF levels after follow-up was investigated. RESULTS: We compared serum HIF-1α and peritoneal fluid CA-125 levels in the three groups receiving peritoneal dialysis treatment. HIF-1α levels increased with peritoneal permeability changes, while CA-125 levels decreased. In patients with high to low permeability changes, HIF-1α levels were higher compared to those with stable or low to high changes, which was statistically significant. Conversely, CA-125 levels significantly decreased in patients whose peritoneal permeability changed from high to low, compared to the other two groups. CONCLUSION: Changes in peritoneal structure can be followed with biomarkers. It has been shown that CA-125 and HIF-1α levels can guide the changes in the peritoneal membrane. This can be useful in the monitoring of peritoneal dialysis.

rAbDesFlow: a novel workflow for computational recombinant antibody design for healthcare engineering.

Recombinant antibodies (rAbs) have emerged as a promising solution to tackle antigen specificity, enhancement of immunogenic potential and versatile functionalization to treat human diseases. The development of single chain variable fragments has helped accelerate treatment in cancers and viral infections, due to their favorable pharmacokinetics and human compatibility. However, designing rAbs is traditionally viewed as a genetic engineering problem, with phage display and cell free systems playing a major role in sequence selection for gene synthesis. The process of antibody engineering involves complex and time-consuming laboratory techniques, which demand substantial resources and expertise. The success rate of obtaining desired antibody candidates through experimental approaches can be modest, necessitating iterative cycles of selection and optimization. With ongoing advancements in technology, in silico design of diverse antibody libraries, screening and identification of potential candidates for in vitro validation can be accelerated. To meet this need, we have developed rAbDesFlow, a unified computational workflow for recombinant antibody engineering with open-source programs and tools for ease of implementation. The workflow encompasses five computational modules to perform antigen selection, antibody library generation, antigen and antibody structure modeling, antigen-antibody interaction modeling, structure analysis, and consensus ranking of potential antibody sequences for synthesis and experimental validation. The proposed workflow has been demonstrated through design of rAbs for the ovarian cancer antigen Mucin-16 (CA-125). This approach can serve as a blueprint for designing similar engineered molecules targeting other biomarkers, allowing for a simplified adaptation to different cancer types or disease-specific antigens.

The diagnostic performance of the Mindray system in detecting CA125 and HE4 for patients with ovarian cancer.

Background: Cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) are the most commonly used tumor biomarkers for ovarian cancer (OC) screening and diagnosis. The risk of ovarian malignancy algorithm (ROMA) score uses these markers, as detected by the Roche system, to predict the risk of OC. This study sought to assess the performance of the Mindray system in detecting CA125 and HE4 for ROMA score calculation in clinical settings. Methods: Consecutive OC patients and patients with benign pelvic masses were screened and enrolled in this study. The CA125 and HE4 levels of these patients were measured using both the Mindray and Roche systems. The ROMA score for each patient was calculated. Diagnostic performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results: The HE4 and CA125 levels were significantly higher in the patients with OC than the patients with benign ovarian masses. Both detection systems showed high efficiency in detecting ovarian cancer. For the premenopausal OC patients, the AUC values for the ROMA score, HE4, and CA125 were 0.866, 0.852, and 0.879, respectively, using the Roche system, and 0.911, 0.902, and 0.883, respectively, using the Mindray system. For the postmenopausal OC patients, the AUC values for the ROMA score, HE4, and CA125 were 0.962, 0.920, and 0.953, respectively, using Roche system, and 0.966, 0.924, and 0.959, respectively, using the Mindray system. The correlation analysis showed strong agreement between the two systems. Among the patients who experienced recurrence, we observed a significant increase in both HE4 and CA125 levels compared to baseline using the Mindray system. Conclusions: The Mindray and Roche systems provide consistent results. The Mindray system can be used to detect HE4 and CA125 for ROMA score calculation.

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.

BACKGROUND: CA-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. METHODS: A 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. RESULTS: The 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. CONCLUSION: The 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.

A dual-center study: can ultrasound radiomics differentiate type I and type II epithelial ovarian cancer patients with normal CA125 levels?

OBJECTIVE: CA125 is recommended by many countries as the primary screening test for ovarian cancer. But there are patients with ovarian cancer having normal CA125. We hope to identify the types of EOC with normal CA125 levels better by building a refined model based on the ultrasound radiomics, thus providing precise medical treatment for patients. METHODS: We included 58 patients with EOC with normal CA125 from 2 centres, who were confirmed by preoperative ultrasound and pathology. We extracted 1130 radiomics features based on the tumour's region of interest from the most typical ultrasound image of each patient. We selected radiomics and clinical features by LASSO and logistic regression to construct Rad-score and clinical models, respectively. Receiver operating characteristic curves judged their test efficacy. On the basis of the combined model, we developed a nomogram. RESULTS: Area under the curves (AUCs) of 0.93 and 0.83 were achieved in both the training and test groups for the combined model. There were similar AUCs between the Rad-score and clinical models of 0.82 and 0.80, respectively. By analysing the calibration curves, it was determined that the nomogram matched actual observations in the training cohort. CONCLUSION: Ultrasound radiomics can differentiate type I and type II EOC with normal CA125 levels. ADVANCES IN KNOWLEDGE: This study is the first to focus on EOC cases with normal level of CA125. The subset of patients constituting 20% of the disease population may require more refined radiomics models.

The value of amide proton transfer imaging combined with serum CA125 levels in predicting lymph vascular invasion in cervical cancer before surgery.

BACKGROUND: Preoperative prediction of lymphovascular space invasion (LVSI) is crucial for improving the prognosis of patients with cervical cancer. PURPOSE: To evaluate the value of preoperative amide proton transfer (APT) imaging combined with serum CA125 levels for predicting LVSI in cervical cancer. MATERIAL AND METHODS: This retrospective study included 80 patients with cervical cancer who underwent preoperative magnetic resonance imaging, including APT imaging. Serum CA125 levels were measured using a fully automated immunoassay analyzer and chemiluminescence method. The presence of LVSI was determined based on the pathological results after surgery. RESULTS: Among the 40 patients who met the requirements, 29 had postoperative pathological confirmation of LVSI, while 11 did not. The areas under the receiver operating characteristic curves (AUC) of preoperative APT and CA125 levels predicting LVSI were 0.889 and 0.687, respectively. When the APT value was 2.9%, the corresponding Youden index was the highest (0.702), with a sensitivity of 79.3% and specificity of 90.9%. When the critical value of the preoperative serum CA15 level was 25.3 u/mL, the corresponding Youden index was the highest (0.508), with a sensitivity of 69.0% and a specificity of 81.8%. The sensitivity and specificity of preoperative APT imaging combined with serum CA125 in predicting LVSI were 82.7% and 100%, respectively, with a Youden's index of 0.828 and an AUC of 0.923. CONCLUSION: The combination of preoperative APT imaging and serum CA125 levels is valuable for predicting LVSI in cervical cancer. Diagnostic efficacy is highest when the APT value is >2.9% and the serum CA125 level is >25.3 u/mL.