On Whether Ca-125 Is the Answer for Diagnosing Overhydration, Particularly in End-Stage Kidney Disease Patients-A Systematic Review.

Overhydration (OH) is a prevalent medical problem that occurs in patients with kidney failure, but a specific marker has still not been found. Patients requiring kidney replacement therapy suffer from a water imbalance, which is correlated with mortality rates in this population. Currently, clinicians employ techniques such as bioimpedance spectroscopy (BIS) and ultrasound (USG) markers of overhydration or markers of heart and kidney function, namely NT-pro-BNP, GFR, or creatinine levels. New serum markers, including but not limited to Ca-125, galectin-3 (Gal-3), adrenomedullin (AMD), and urocortin-2 (UCN-2), are presently under research and have displayed promising results. Ca-125, which is a protein mainly used in ovarian cancer diagnoses, holds great potential to become an OH marker. It is currently being investigated by cardiologists as it corresponds to the volume status in heart failure (HF) and ventricular hypertrophy, which are also associated with OH. The need to ascertain a more precise marker of overhydration is urgent mainly because physical examinations are exceptionally inaccurate. The signs and symptoms of overhydration, such as edema or a gradual increase in body mass, are not always present, notably in patients with chronic kidney disease. Metabolic disruptions and cachexia can give a false picture of the hydration status. This review paper summarizes the existing knowledge on the assessment of a patient's hydration status, focusing specifically on kidney diseases and the role of Ca-125.

D-dimer, Fibrinogen and Tumor Marker Levels in Patients with benign and Malignant Ovarian Tumors.

Limited studies have investigated the differences between the levels of plasma coagulants and tumor markers in ovarian cancer. Therefore, we conducted this study to determine and compare the level of coagulation, fibrinolysis and tumor markers in patients with benign and malignant ovarian tumors. This cross-sectional study was conducted between January 2022 and February 2023 in Imam Hossein Hospital on patients with ovarian mass. Laboratory tests included platelet count, PT, INR, PTT, fibrinogen and D-dimer were sent to the pathology laboratory to be examined by a pathologist. Based on histopathology, patients were divided into benign, borderline and malignant groups. Logistic regression was used for determine predictors of malignancy. Receiver operating characteristics (ROC) curves and their corresponding 95% CI were determined for the predictor value of the full model. From 141 investigated patients, tumor type in 124 (87.94%) patients were benign, in 12 (8.51%) was malignant and in 5 (3.55%) was borderline. D-dimer, Ca-125 and HE4 were significantly higher in the patients with malignant tumor type (P<0.001), whereas AFP was significantly higher in patients with borderline tumor type (P<0.001). With one-unit increase in D-dimer odds of borderline/malignant tumor 0.3% increases (OR=1.003, 95% CI: 1.001, 1.006) and with one-unit increase in Ca-125 odds of borderline/malignant tumor 1% increases (OR=1.01, 95% CI: 1.003, 1.02). We found that plasma fibrinogen, D-dimer and Ca-125 levels are independently associated with malignant ovarian tumors and combined use of these markers has the high discriminant power for distinction of benign and malignant ovarian masses.
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Serum CA-125 as a predictor in the early diagnosis of ectopic pregnancy in Vietnam - A case-control study.

INTRODUCTION: This study aimed to determine the predictive value of cancer antigen-125 (CA-125) in combination with serum beta-human chorionic gonadotropin (ß-hCG) and progesterone in the early detection of ectopic pregnancy (EP). METHODS: Between May 2019 and May 2020, the cross-sectional study recruited 42 cases of EP and 42 cases of IUP at the same gestational age who visited the Department of Obstetrics and Gynecology, Hospital of Hue University of Medicine and Pharmacy. EP was diagnosed based on surgical (laparoscopy) and postoperative pathology examination. RESULTS: There were significant differences of mean level of ß-hCG (2570 mUI/mL vs. 18357.7 mUI/mL), progesterone (10.79 ± 8.16 ng/ml vs. 27.42 ± 4.17 ng/ml) and CA-125 (26.90 ± 10.26 U/mL vs. 70.61 ± 20.89 U/mL) between the EP and the IUP groups (p < 0.001). In the prediction of early diagnosis of EP, the cut-off value of CA-125 at 30.94 U/mL has a sensitivity of 89.3% and a specificity of 87,9%; the cut-off value of ß hCG at 2750mIU/ml has the sensitivity of 75%, specificity of 78,8%; the cut-off value of progesterone at 10.24 ng/mL has the sensitivity of 85.7%, specificity of 81.8%. A combination of CA-125, ß hCG, and progesterone had a sensitivity of 92.8% and a specificity of 90.9% in early diagnosis of EP. DISCUSSION: Serum CA-125 levels can be used independently or in combination with other markers in the early diagnosis of EP.

CA125 como nuevo biomarcador en pacientes con circulación de Fontan / CA125: a new biomarker in patients with Fontan circulation

Introducción y objetivos Los pacientes con circulación de Fontan (CF) presentan una gran incidencia de complicaciones y ningún biomarcador estratifica el riesgo. El objetivo es analizar la asociación de biomarcadores con un perfil clínico de disfunción de la CF, incluyendo por primera vez el antígeno carbohidrato 125 (CA125), y proponer una estimación del riesgo basada en la combinación de biomarcadores. Métodos Estudio transversal de adultos con CF. Se consideró perfil clínico desfavorable el combinado de insuficiencia cardiaca, arritmias auriculares, fístulas venovenosas, enteropatía pierdeproteínas o bronquitis plástica. Se analizaron variables clínicas y analíticas, incluidos CA125, NT-proBNP, función renal y hepática y amplitud de distribución eritrocitaria (ADE). Se realizó un estudio univariado y multivariado de la relación de dichas complicaciones clínicas y curvas ROC para obtener puntos de corte. Resultados Se incluyó a 56 pacientes (media de edad, 27,4±7,8 años). El 34% tenía un perfil clínico desfavorable, con valores de CA125 significativamente mayores (30,1 frente a 12,6 UI/ml; p=0,001). LnCA125 (OR=5,1; IC95%, 1,2-22), ADE (OR=1,8; IC95%, 1,1-3.1) y FIB4 (OR=38; IC95%, 1,7-855) se asociaron con un perfil de disfunción clínica. Los puntos de corte fueron CA125 ≥ 20 U/ml, FIB4 ≥ 0,75 y ADE ≥ 14,5%, y la probabilidad de un perfil clínico desfavorable fue del 81% con 2 o más biomarcadores elevados. Conclusiones El aumento de CA125 se asocia con mayor prevalencia de complicaciones en pacientes con CF. Los valores de CA125 ≥ 20 U/ml, FIB4 ≥ 0,75 y ADE ≥ 14,5% identifican con alta probabilidad fracaso clínico de la CF. (AU)

Introduction and objectives Patients with Fontan circulation (FC) have a high incidence of clinical complications. However, no biomarker is able to accurately stratify risk. The aim of this study was to analyze the relationship between biomarkers and clinical complications, including carbohydrate antigen 125 (CA125) for the first time, and to propose a risk estimation based on a combination of biomarkers. Methods Cross-sectional study of patients with FC. The clinical endpoint was the combination of heart failure, atrial arrhythmias, veno-venous fistulae, protein-losing enteropathy, or plastic bronchitis. Demographic, clinical, and laboratory variables were analyzed, including CA125, NT-proBNP, renal and liver function, and red cell distribution width (RDW). We performed univariate and multivariate analyses of the relationship between these variables and the composite endpoint. Cutoff values were calculated by ROC curves. Results We included 56 patients (27.4±7.8 years). A total of 34% showed the composite endpoint, with significantly higher CA125 levels (30.1 IU/mL vs 12.6 IU/mL; P=.001). In the multivariate model, the biomarkers related to the endpoint were LnCA125 (OR, 5.1; 95%CI, 1.2-22), RDW (OR, 1.8; 95%CI, 1.1-3.1), and FIB4 (OR, 38, 95%CI, 1.7-855). The cutoff points were CA125 ≥ 20 U/mL, FIB4 ≥ 0.75, and RDW ≥ 14.5%, and the probability of the occurrence of the endpoint was 81% if ≥ 2 biomarkers were elevated. Conclusions CA125 elevation is associated with a higher prevalence of complications in patients with Fontan-type circulation. CA125 levels ≥ 20U/mL, FIB4 ≥ 0.75 and RDW ≥ 14.5% identify with a high probability the clinical failure of FC. (AU)

Prognostic significance of serum CA125 in the overall management for patients with gastrointestinal stromal tumors.

BACKGROUND: Carbohydrate antigen 125 (CA125) is elevated as a tumor marker in many carcinomas, but its association with gastrointestinal stromal tumor (GIST) has received less attention. This study intends to evaluate whether CA125 level can predict tumor progression and overall survival (OS) of GIST patients. METHODS: We retrospectively analyzed the clinical data and follow-up records of GIST patients who underwent surgical resection in Nanjing Drum Tower Hospital from August 2010 to December 2020. All patients were classified according to serum CA125 level. The relationship between CA125 and clinical outcomes was then examined. RESULTS: A total of 406 GIST patients were enrolled in this study, among which 46 patients had preoperative elevated serum CA125 level and 13 patients with high CA125 level both preoperative and postoperative were observed. Preoperative CA125 concentration was significantly related to rupture status, resection style, tumor site, tumor size, mitotic index, NIH risk grade and c-kit exons. According to Kaplan-Meier curve analysis, high expression of postoperative CA125 was significantly correlated with worse progression-free survival (PFS) and OS among patients with preoperative elevated CA125 level. Ultimately, Cox proportional regression model analysis revealed that increase of preoperative and concurrent postoperative CA125 concentration was an independent predictive factor for PFS. CONCLUSIONS: The concurrent abnormality of serum CA125 before and after operation was an independent risk factor for GIST progression, suggesting its significance as a serum biomarker in the overall management of GIST patients.

Serum kisspeptin levels in deep-infiltrating, ovarian, and superficial endometriosis: A prospective observational study.

The diagnosis of endometriosis may delay for many years due to non-deterministic symptoms and avoiding surgical interventions. Kisspeptins are hormones that interact with endometrial tissue to limit invasions during placentation and various cancers and are suggested to be also associated with endometriosis. This study evaluated if serum kisspeptin levels are associated with the invasion depth in endometriosis. Forty patients between 18 and 45 years of age and admitted to a tertiary-care Obstetrics and Gynecology Department between 2020 and 2021 with a diagnosis of endometriosis, and 40 patients without endometrioma were included in the study. Demographic, obstetric, clinical, and biochemical characteristics were evaluated in patients with superficial (SE) and deep infiltrating (DIE) endometriosis and healthy controls. Twenty patients (50%) had SE, 14 (35%) had DIE, and 22 (55%) had endometrioma in the patient group. Fertility rates were higher among controls, but similar between patients with SE and DIE. CA125 levels were significantly higher in the DIE group. SE and DIE groups had similar kisspeptin values, significantly higher than controls. CA125 and kisspeptin levels were not correlated in study groups. Serum kisspeptin levels were significantly different between endometriosis patients and healthy controls. However, kisspeptin levels were unable to differentiate endometriosis severity. Our results suggest that kisspeptins might play a role in the pathogenesis of endometriosis, which needs further assessment in more comprehensive studies.

The study of serum C-reactive protein, Serum cystatin C, and carbohydrate antigen 125 in patients with acute ischemic stroke.

Stroke is the most common, deadly, and complicating neurological disease. Many studies have shown that the levels of some acute inflammatory reactants in people with ischemic stroke are higher than average. Therefore, in this study, three acute inflammatory reactants, i.e., C-reactive protein, Serum cystatin C, and carbohydrate antigen 125, were evaluated in patients with acute ischemic stroke to consider the association between these serums with intra and extra-cerebral vessels stenosis. In this cross-sectional study, 90 patients with non-embolic ischemic stroke were evaluated. The diagnosis was by physical examination, rejection of emboli, and brain imaging. Blood samples were taken in the first 24 hours of a stroke. ELISA test was used to measure CRP, Serum cystatin C, and CA125. Doppler ultrasound of cerebral arteries was also performed in the first five days. Independent chi-square and t-tests were used to analyze the data. The result of CRP level in patients with stenosis was 7.58±1.33µg/ml and in patients without stenosis was 4.10±1.75µg/ml (p = 0.004). Also, there was a significant relationship between serum CRP level and stenosis (p = 0.003). In patients with abnormal CRP, the internal carotid artery, middle cerebral artery, and anterior cerebral artery were the most involved. In patients with normal CRP, the most involved arteries were the anterior cerebral artery, internal carotid artery, and middle cerebral artery, respectively. There was a significant relationship between serum CRP level and the location of internal carotid artery stenosis (p = 0.015) and middle cerebral artery (p = 0.006). The amount of cystatin C between the normal CRP and abnormal CRP groups was statistically significant so that its concentration in the normal group was less than in the abnormal group (p = 0.04). The results of measuring the serum concentration of carbohydrate antigen 125 showed that the serum level in the normal group was statistically lower than in the abnormal group (P = 0.02). The results showed that stenosis of the internal carotid artery and middle cerebral artery is more common in patients with ischemic stroke with high serum CRP levels. This finding suggests that abnormal CRP may be more associated with narrowing some cerebral arteries.

Extremely high serum CA19-9 level along with elevated D-dimer in assisting detection of ruptured ovarian endometriosis.

BACKGROUND: To clarify clinical importance of serum CA19-9, CA-125, and plasma D-dimer (D-D) levels in detecting spontaneously ruptured ovarian endometriosis (OE). MATERIALS AND METHODS: We retrospectively examined 173 patients with endometriosis out of 735 cases of OE between 2013 and 2019. Among these, 21 cases were diagnosed as "spontaneously ruptured" after surgery, while the remaining cases were unruptured. Venous blood was collected pre-operatively to detect CA19-9, CA-125, and D-D levels. A receiver operating characteristic curve analysis was applied to test clinical value of each marker. RESULTS: Among the 21 patients with ruptured OE, 16 had a history of pelvic cysts, 19 claimed sudden onsets of lower abdominal pain, and fluid accumulation were detected in cul-de-sac in only six participants by ultrasound. For serological investigation, both CA19-9 and D-D were significantly elevated in the ruptured OE group (343.09 ± 367.67 U/ml vs. 36.84 ± 40.01 U/ml, 3.39 ± 4.90 mg/L vs. 0.43 ± 0.29 mg/L, both p < .0001). The area under curve (AUC) value for the combination of CA19-9 and D-D was 0.975 (95% CI, 0.939 - 0.993), with specificity of 96.69%, and sensitivity of 85.71%. The combination of CA-125, CA19-9 and D-D showed the highest AUC value that up to 0.976 (95% CI, 0.940-0.993), with sensitivity of 95.24%, and specificity of 87.50%. CONCLUSION: The combination of CA19-9 and D-D can be chosen as an effective and economical indicators to identify patients with spontaneously ruptured OE in pre-operation assessment. However, from the perspective of differential diagnosis, the combination of CA-125, CA19-9 and D-D is the best choice. Key messagesTaking into account the economic effect, the combination of CA19-9 and D-D can be chosen as an effective indicators to identify patients with spontaneously ruptured OE in pre-operation assessment.From the perspective of differential diagnosis, the combination of CA-125, CA19-9 and D-D is the best choice to identify patients with spontaneously ruptured OE.

Punto de corte óptimo del antígeno carbohidrato 125 para la identificación de pacientes con bajo riesgo tras un ingreso por insuficiencia cardiaca aguda / Optimal carbohydrate antigen 125 cutpoint for identifying low-risk patients after admission for acute heart failure

Introducción y objetivos: El antígeno carbohidrato 125 (CA125) se ha mostrado útil para la estratificación del riesgo de los pacientes ingresados por insuficiencia cardiaca aguda (ICA). Se intenta determinar un punto de corte para identificar a los pacientes con bajo riesgo de muerte y muerte/reingreso por insuficiencia cardiaca 1 mes tras el ingreso por ICA. Métodos: La cohorte de derivación incluyó a 3.231 pacientes con ICA consecutivos. Se identificaron valores de corte de CA125 con un valor predictivo negativo (VPN) del 90% y una sensibilidad de hasta el 85%. La idoneidad de estos puntos de corte y el riesgo de muerte/reingreso al mes se evaluaron mediante el método de Royston-Parmar. Se seleccionó el mejor punto de corte y se validó en una cohorte del BIOSTAT-CHF (n=1.583). Resultados: En la cohorte de derivación, la mediana [intervalo intercuartílico] de CA125 fue 57 [25,3-157] U/ml. El punto de corte óptimo fue <23 U/ml (el 21,5% de los pacientes), con VPN de muerte y del objetivo compuesto del 99,3 y el 94,1% respectivamente. En los análisis multivariables, el CA125 <23 U/ml se asoció con un menores riesgos de muerte (HR=0,20; IC95%, 0,08-0,50; p <0,001) y del objetivo combinado (HR=0,63; IC95%, 950,45-0,90; p=0,009). Su capacidad para discriminar a los pacientes con riesgo bajo a 1 mes se confirmó en la cohorte de validación (VPN de muerte y del objetivo compuesto, el 98,6 y el 96,6%). La capacidad predictiva seguía siendo significativa a los 6 meses de seguimiento. Conclusiones: En pacientes ingresados por ICA, el CA125 <23 U/ml identificó un subgrupo de pacientes con bajo riesgo de eventos clínicos adversos a corto plazo que pueden no requerir un seguimiento estrecho (AU)

Introduction and objectives: Carbohydrate antigen 125 (CA125) has been shown to be useful for risk stratification in patients admitted with acute heart failure (AHF). We sought to determine a CA125 cutpoint for identifying patients at low risk of 1-month death or the composite of death/HF readmission following admission for AHF. Methods: The derivation cohort included 3231 consecutive patients with AHF. CA125 cutoff values with 90% negative predictive value (NPV) and sensitivity up to 85% were identified. The adequacy of these cutpoints and the risk of 1-month death/HF readmission was then tested using the Royston-Parmar method. The best cutpoint was selected and externally validated in a cohort of patients hospitalized from BIOSTAT-CHF (n=1583). Results: In the derivation cohort, the median [IQR] CA125 was 57 [25.3-157] U/mL. The optimal cutoff value was <23 U/mL (21.5% of patients), with NPVs of 99.3% and 94.1% for death and the composite endpoint, respectively. On multivariate survival analyses, CA125 <23 U/mL was independently associated with a lower risk of death (HR, 0.20; 95%CI, 0.08-0.50; P <.001), and the combined endpoint (HR, 0.63; 95%CI, 950.45-0.90; P=.009). The ability of this cutpoint to discriminate patients at a low 1-month risk was confirmed in the validation cohort (NPVs of 98.6% and 96.6% for death and the composite endpoint). The predicted ability of this cutoff remained significant at 6 months of follow-up. Conclusions: In patients admitted with AHF, CA125 <23 U/mL identified a subgroup at low risk of short-term adverse events, a population that may not require intense postdischarge monitoring (AU)

Serum CCAT2 as a biomarker for adjuvant diagnosis and prognostic prediction of cervical cancer.

Growing evidence indicates that lncRNA colon cancer-associated transcript 2 (CCAT2) is associated with cancers. However, the clinical value of CCAT2 in cervical cancer (CC) remains unclear. In this study, serum CCAT2 level was detected by real-time quantitative PCR (RT-qPCR). Carbohydrate antigen 125 (CA125) and squamous-cell carcinoma antigen (SCC) were detected by electrochemiluminescence. A receiver operating characteristic (ROC) curve was utilized to estimate the diagnostic efficiency of CCAT2. Kaplan-Meier survival analysis and univariable and multivariable analyses were performed to assess the prognostic value of CCAT2. The relative expression level of CCAT2 in primary CC patients was significantly higher than that in cervical intraepithelial neoplasias (CIN) patients and healthy controls (both P < 0.001). CCAT2 relative expression was positively correlated with tumor Federation of Gynecology and Obstetrics (FIGO) stage, SCC-Ag and lymph node metastasis (LNM) (all P < 0.05). CCAT2 expression in recurrent/metastatic CC was significantly higher compared with primary CC (P < 0.0001) or operated CC (P < 0.0001) and during follow-up, CCAT2 expression was increased before surgery and decreased significantly after surgery (P < 0.0001). Furthermore, the overall survival rate of CC patients with high CCAT2 expression group markedly decreased as compared with that of low CCAT2 expression group (P = 0.026). Univariate analyses indicated that CCAT2 was a poor prognostic factor associated with overall survival (OS). Our study indicates that CCAT2 may be valuable in complementary diagnosis and monitoring of progression and prognosis of CC patients. Combined detection of CCAT2, CA125 and SCC can greatly improve the diagnostic efficiency of primary CC.

A prognostic model of patients with ovarian mucinous adenocarcinoma: a population-based analysis.

BACKGROUND: Ovarian mucinous carcinoma is a disease that requires unique treatment. But for a long time, guidelines for ovarian serous carcinoma have been used for the treatment of ovarian mucinous carcinoma. This study aimed to construct and validate nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with ovarian mucinous adenocarcinoma. METHODS: In this study, patients initially diagnosed with ovarian mucinous adenocarcinoma from 2004 to 2015 were screened from the Surveillance, Epidemiology, and End Results (SEER) database, and divided into the training group and the validation group at a ratio of 7:3. Independent risk factors for OS and CSS were determined by multivariate Cox regression analysis, and nomograms were constructed and validated. RESULTS: In this study, 1309 patients with ovarian mucinous adenocarcinoma were finally screened and randomly divided into 917 cases in the training group and 392 cases in the validation group according to a 7:3 ratio. Multivariate Cox regression analysis showed that the independent risk factors of OS were age, race, T_stage, N_stage, M_stage, grade, CA125, and chemotherapy. Independent risk factors of CSS were age, race, marital, T_stage, N_stage, M_stage, grade, CA125, and chemotherapy. According to the above results, the nomograms of OS and CSS in ovarian mucinous adenocarcinoma were constructed. In the training group, the C-index of the OS nomogram was 0.845 (95% CI: 0.821-0.869) and the C-index of the CSS nomogram was 0.862 (95%CI: 0.838-0.886). In the validation group, the C-index of the OS nomogram was 0.843 (95% CI: 0.810-0.876) and the C-index of the CSS nomogram was 0.841 (95%CI: 0.806-0.876). The calibration curve showed the consistency between the predicted results and the actual results, indicating the high accuracy of the nomogram. CONCLUSION: The nomogram provides 3-year and 5-year OS and CSS predictions for patients with ovarian mucinous adenocarcinoma, which helps clinicians predict the prognosis of patients and formulate appropriate treatment plans.

High expression of TRIM24 predicts worse prognosis and promotes proliferation and metastasis of epithelial ovarian cancer.

BACKGROUND: Tripartite Motif-Containing 24 (TRIM24) is a member of the tripartite motif family. TRIM24 is claimed aberrantly activated in a number of cancers, such as breast cancer, prostate cancer and lung cancer. However, the expression of TRIM24 in epithelial ovarian cancer (EOC) and its relationship with prognosis remain unclear. In this study, we investigated the expression pattern and underlying clinical significance of TRIM24 in EOC. RESULTS: Data from Oncomine and immunohistochemistry of tissue samples demonstrated that TRIM24 expression was obviously elevated in ovarian carcinoma compared with normal ovary tissues. Elevated TRIM24 expression was closely correlated with serum CA-125 (P = 0.0294), metastasis (P = 0.0022), FIGO (International Federation of Gynecology and Obstetrics) stage (P = 0.0068) and Ki-67 level (P = 0.0395). Kaplan-Meier survival analysis found that TRIM24 expression increased inversely with the clinical prognosis of patients with EOC. Moreover, colony formation and CCK-8 assays showed that TRIM24 promoted EOC cell growth, and tumorigenic experiments in nude mice showed that TRIM24 knockdown inhibited tumor growth in vivo. The Spearman's correlations revealed that the expression of TRIM24 was significantly correlated with levels of Ki-67 (P = 0.01), at a correlation coefficient of 0.517. Wound-healing and transwell migration assays demonstrated TRIM24 facilitated cell migration. Mechanism studies showed that TRIM24 could promote the phosphorylation level of Akt and the process of EMT. CONCLUSION: Our results confirmed that TRIM24 could predict poor prognosis of EOC patients and promote tumor progression by regulating Akt pathway and EMT. TRIM24 may be used as a new prognostic marker for EOC and may provide a new strategy for targeted therapy of epithelial ovarian cancer.

Application of a novel microscopic technique for quantifying CA125 binding to circulating mononuclear cells in longitudinal specimens during treatment for ovarian cancer.

BACKGROUND: Measurement of serum CA125, an antigenic fragment of human mucin 16 (MUC16), is used to monitor the clinical progression of epithelial ovarian cancer (EOC). However, rather than simply a passive marker reflecting tumor burden, MUC16 may have a more active role by binding to immune cells and altering their tumor response. We developed a research tool to measure MUC16-binding to the surfaces of peripheral blood mononuclear cell (PBMC) subtypes and tested its research value using specimens collected serially from a woman being treated for high grade serous EOC. METHODS: Cryopreserved PBMCs were mixed with anti-CA125 antibody-labeled plasmonic gold nanoparticles (PNPs) to detect cell surface MUC16-binding along with fluorescent stains to identify B cells, NK cells, NK-T cells, T cells, and monocytes. From 3D darkfield images, a computer algorithm was applied to enumerate PNP-binding and fluorescence microscopy to identify cell lineage. Average MUC16-binding was determined by fitting a Poisson distribution to PNP-counts across similar cell types. MUC16-binding to cell types was correlated with treatment details, CA125 levels, and complete blood count (CBC) data. RESULTS: Over a 21-month period, monocytes had the highest level of MUC16-binding which was positively correlated with serum CA125 and inversely correlated with circulating monocyte and lymphocyte counts. Fluctuations of PNP-binding to NK cells were associated temporally with types of chemotherapy and surgical events. Levels of MUC16 bound to NK cells were positively correlated with levels of MUC16 bound to T and NK-T cells and inversely correlated with circulating platelets. CONCLUSIONS: Assessment of MUC16-binding among cryopreserved PBMC cell types can be accomplished using darkfield and fluorescence microscopy. Correlations observed between level of binding by cell type with serum CA125, CBC data, and treatment details suggest that the new techniques may offer novel insights into EOC's clinical course.

Sister Mary Joseph nodule as cutaneous manifestations of metastatic ovarian cancer: A case report and review of the literature.

RATIONALE: The Sister Mary Joseph's nodule is an umbilical nodule resulting from the metastasis of malignant tumors in the pelvic and/or abdominal cavity. Sister Mary Joseph's nodules are very rare, and the morphology of the skin lesions is not specific and is easily misdiagnosed. Here, we report a case of cutaneous manifestations of metastatic ovarian cancer. PATIENT CONCERNS: The patient was admitted to our hospital because of abdominal distention, and a nodule was found in the umbilicus. A computerized tomography scan of the entire abdomen showed nodular soft tissue in the subcutaneous fat space of the umbilical area and multiple pelvic masses, which were suspected metastases of peritoneal and omentum ovarian cancer. INTERVENTIONS: To confirm the pathological diagnosis, posterior fornix puncture was performed. Pathological biopsy showed adenocarcinoma. Histological examination revealed a mass arising from high-grade serous carcinoma of the ovary. The patient received 2 cycles of chemotherapy with paclitaxel liposomes and carboplatin and underwent interval debulking surgery. Postoperative pathology was consistent with high-grade serous carcinoma of the ovary. Cancer involvement was observed in umbilical lesions. After the operation, the patient was given 6 cycles of chemotherapy with paclitaxel liposomes and carboplatin. OUTCOMES: The patient underwent follow-up until October 2020. A computerized tomography scan of the entire abdomen showed that the lymph nodes in the abdominal cavity were larger than before, suggesting a platinum-sensitive relapse. After receiving the same regimen of chemotherapy, carbohydrate antigen 125 dropped to the normal range, and consolidated treatment was administered for 3 cycles. Owing to her BRCA1 mutations, olaparib was administered for maintenance treatment. Until now, she had been in the outpatient clinic for regular follow-up visits. LESSONS: The umbilicus remains an infrequently examined area, which cannot be underestimated and warrants careful clinical follow-up and histological evaluation, as appropriate.

Genome-wide association study of serum tumor markers in Southern Chinese Han population.

BACKGROUND: Serum indicators AFP, CA50, CA125, CA153, CA19-9, CEA, f-PSA, SCC-Ag have been confirmed as tumor markers (TMs). We conducted a genome-wide association study on 8 tumor markers of our 427 Han population in southern China, in order to identify genetic loci that are significantly associated with the level of 8 tumor markers. METHODS: We use Gene Titan multi-channel instrument and Axiom Analysis Suite 6.0 software for genotyping. We used IMPUTE2 software for imputation, and 1000 Genomes Project (Phase 3) was used as haplotype reference. After necessary quality control and statistical analysis, genetic loci genome-wide associated with TMs (p < 5E-8) will be identified. Finally, we selected Top SNPs (p < 5E-7) from the GWAS results for replication test. We used SPSS software to draw the distribution box plots of serum TMs under different genotypes of significant loci. RESULTS: The results showed that there were only MUC1 (mucin 1)-rs4072037 significantly genome-wide associated with CA153 (p = 1.28E-18). However, we found that a total of 30 genetic loci have a suggestively significant genome-wide association with the level of 8 serum tumor markers (p < 5E-6). Then 3 Top SNPs (p < 5E-7) were selected for replication verification. The results showed that MUC1-rs4072037 was still significantly associated with CA153 in another population (p = 3.73E-08). Comparing with the TT genotype of rs4072037, the CA153 level was higher under CC or CT genotype of rs4072037. CONCLUSION: MUC1-rs4072037 is significantly genome-wide associated with CA153 level. There are 30 genetic loci suggestively genome-wide associated with level of tumor markers among the Han population from Southern China.

Detection of plasma exosomal miRNA-205 as a biomarker for early diagnosis and an adjuvant indicator of ovarian cancer staging.

BACKGROUND: Ovarian cancer (OC) is one of the serious threats to the health of women worldwide, and accurate biomarkers are urgently demanded for early diagnosis of OC. We have previously confirmed that miR-205 promotes the invasion and metastasis of OC cells by inhibiting the expression of the tumor suppressor gene TCF21. In this study, we used liquid biopsy technology to detect the expression levels of the four genes, miR-205, CA125, HE4 and TCF21, in the exosomes of plasma of OC patients. Combined with analysis of clinicopathological parameters of OC patients, we aimed to provide efficient and non-invasive laboratory biomarkers for early diagnosis of OC. METHODS: 36 OC patients who were diagnosed in local hospitals from September 2020 to July 2021 were selected as OC group, 31 cases of surgically diagnosed with ovarian benign lesions were selected as benign group, and 32 healthy people who underwent physical examination during the same period were selected as a control group. We employed transmission electron microscope (TEM), Western blotting (WB), and nanoparticle tracking analysis (NTA) to identify biomarkers in the exosomes extracted from plasma of the three groups. The RNA levels of miR-205, CA125, HE4 and TCF21 genes in plasma exosomes were detected by real-time quantitative PCR (qRT-PCR) method. We used clinical pathological parameters and the Receiver Operating Characteristic (ROC) curves to evaluate the diagnostic efficacy for the genes detected in plasma exosomes. RESULTS: We found that the expression level of miR-205 in plasma exosomes of the OC group was significantly higher than that of the benign and control groups (P <  0.05), and the level of miR-205 was elevated during the III-IV periods of OC and lymph node metastasis. CONCLUSION: The level of miR-205 in plasma exosomes is a valuable tumor biomarker to improve OC diagnosis.

Correlation of Preoperative Serum and Intraoperative Peritoneal Lavage Fluid Ca-125 Levels with Postoperative Tumor Histology in Patients with Endometrial Cancer: A Prospective-Controlled Study.

BACKGROUND: The role of Ca-125 in endometrial cancer is not fully known. Some authors have reported high Ca-125 levels in patients with recurrent or advanced endometrial cancer, whereas others have stated that Ca-125 levels and the advance of the disease were not correlated in endometrial cancer. This makes it inevitable for clinicians to search for different measurement methods or interpretation of the present tumor markers. The aim of this study was to evaluate the relationship between Ca-125 values of the serum and abdominal lavage fluid and postoperative histopathological parameters in patients with endometrial carcinoma. METHODS: The study included patients who were diagnosed with endometrial cancer in the Gynecology Clinic and were planned to undergo surgery. The correlations of clinicopathological parameters with preoperative values of Ca-125 measured from serum and abdominal lavage fluid were investigated. The Spearman correlation test was applied in the analysis of correlations of serum and abdominal lavage fluid Ca-125 values with postoperative tumor characteristics. RESULTS: The serum Ca-125 values were determined to be positively correlated with surgical stage, tumor diameter, and lymph node involvement (p = 0.03; p = 0.04; and p = 0.01, respectively). No correlation was determined between tumor grade and serum Ca-125 level. The level of Ca-125 in the abdominal lavage fluid was observed to be correlated with surgical stage and tumor grade, but not with tumor diameter or lymph node involvement (p = 0.01, p = 0.04, respectively). CONCLUSIONS: The value of Ca-125 in the abdominal lavage fluid has a positive correlation with the surgical stage and tumor grade in patients with endometrial carcinoma.

Application value of the treatment of breast cancer bone metastases with radioactive seed 125I implantation under CT-guidance.

BACKGROUND: To investigate the application value of the treatment of breast cancer bone metastases with radioactive seed 125I implantation under CT-guidance. METHODS: A total of 90 patients with breast cancer admitted to our hospital from January 2017 to January 2018 were selected as the research objects and were divided into control group and experimental group according to random grouping, with 45 cases in each group. Conventional treatment was used in the control group, while the treatment of radioactive seed 125I implantation under CT-guidance was used in the experimental group. The clinical efficacy, pain intensity and levels of carcinoembryonic antigen (CEA), carcinoembryonic antigen 153 (CA153), carbohydrate antigen (CA125) in the two groups were compared. RESULTS: As for the pain intensity, it was evidently lower in the experimental group after treatment than that in the control group (P < 0.05); as for the total effective rate, it was obviously higher in the experimental group after treatment than that in the control group (P < 0.05); as for the levels of CEA, CA153 and CA125, the data in the experimental group after treatment were much lower than the control group (P < 0.05). CONCLUSION: Radioactive seed 125I implantation under CT-guidance can effectively improve the effect of the treatment of breast cancer bone metastases. It has curative efficacy and it is worth promoting and using.

Prognostic Value of Combined Lactate Dehydrogenase, C-Reactive Protein, Cancer Antigen 153 and Cancer Antigen 125 in Metastatic Breast Cancer.

BACKGROUND: Breast cancer (BC), especially metastatic BC, is one of the most lethal diseases in women. CA 125 and CA 15-3 are commonly used indicators for diagnosis and prognosis of BC. Some serological indicators, such as lactate dehydrogenase (LDH) and C-reactive protein (CRP), can also be used to assess the prognosis and progression in BC. METHODS: Univariate Cox regression analysis and LASSO regression analysis were performed to identify prognostic factors and build prognostic models. We distributed the patients into 2 groups based on the median risk score, analyzed prognosis by Kaplan-Meier curve, and screened independent prognostic factors by multivariate Cox regression analysis. RESULT: We identified 4 indicators-LDH, CRP, CA 15-3, and CA 125-related to the prognosis in BC and established a prognostic model. The high LDH group showed worse overall survival (OS) than low LDH group (P = .017; hazard ratio (HR), 1.528; 95% confidence interval (CI), 1.055-2.215). The high CRP group showed worse OS than low CRP group (P = .004; HR, 1.666; 95% CI, 1.143-2.429). The high CA153 group showed worse OS than low CA 15-3 group (P=.011; HR, 1.563; 95% CI, 1.075-2.274). The high CA 125 group showed worse OS than low CA 125 group (P = .021; HR, 1.499; 95% CI, 1.031-2.181). The area under the curve for risk score was .824, Ki-67 was .628, age was .511, and grade was .545. Risk score was found to be an independent prognostic factor using multivariate Cox regression analysis. CONCLUSION: We successfully established an optimization model by combining 4 prognosis-related indicators to assess the prognosis in patients with metastatic BC.