Diagnosing and staging epithelial ovarian cancer by serum glycoproteomic profiling.

BACKGROUND: There is a need for diagnostic tests for screening, triaging and staging of epithelial ovarian cancer (EOC). Glycoproteomics of blood samples has shown promise for biomarker discovery. METHODS: We applied glycoproteomics to serum of people with EOC or benign pelvic masses and healthy controls. A total of 653 analytes were quantified and assessed in multivariable models, which were tested in an independent cohort. Additionally, we analyzed glycosylation patterns in serum markers and in tissues. RESULTS: We identified a biomarker panel that distinguished benign lesions from EOC with sensitivity and specificity of 83.5% and 90.1% in the training set, and of 86.7 and 86.7% in the test set, respectively. ROC analysis demonstrated strong performance across a range of cutoffs. Fucosylated multi-antennary glycopeptide markers were higher in late-stage than in early-stage EOC. A comparable pattern was found in late-stage EOC tissues. CONCLUSIONS: Blood glycopeptide biomarkers have the potential to distinguish benign from malignant pelvic masses, and early- from late-stage EOC. Glycosylation of circulating and tumor tissue proteins may be related. This study supports the hypothesis that blood glycoproteomic profiling can be used for EOC diagnosis and staging and it warrants further clinical evaluation.

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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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.

Quantitative analysis of the MRI features in the differentiation of benign, borderline, and malignant epithelial ovarian tumors.

OBJECTIVE: This study aims to investigate the value of the quantitative indicators of MRI in the differential diagnoses of benign, borderline, and malignant epithelial ovarian tumors (EOTs). MATERIALS AND METHODS: The study population comprised 477 women with 513 masses who underwent MRI and operation, including benign EOTs (BeEOTs), borderline EOTs (BEOTs), and malignant EOTs (MEOTs). The clinical information and MRI findings of the three groups were compared. Then, multivariate logistic regression analysis was performed to find the independent diagnostic factors. The receiver operating characteristic (ROC) curves were also used to evaluate the diagnostic performance of the quantitative indicators of MRI and clinical information in differentiating BeEOTs from BEOTs or differentiating BEOTs from MEOTs. RESULTS: The MEOTs likely involved postmenopausal women and showed higher CA-125, HE4 levels, ROMA indices, peritoneal carcinomatosis and bilateral involvement than BeEOTs and BEOTs. Compared with BEOTs, BeEOTs and MEOTs appeared to be more frequently oligocystic (P < 0.001). BeEOTs were more likely to show mild enhancement (P < 0.001) and less ascites (P = 0.003) than BEOTs and MEOTs. In the quantitative indicators of MRI, BeEOTs usually showed thin-walled cysts and no solid component. BEOTs displayed irregular thickened wall and less solid portion. MEOTs were more frequently characterized as solid or predominantly solid mass (P < 0.001) than BeEOTs and BEOTs. The multivariate logistic regression analysis showed that volume of the solid portion (P = 0.006), maximum diameter of the solid portion (P = 0.038), enhancement degrees (P < 0.001), and peritoneal carcinomatosis (P = 0.011) were significant indicators for the differential diagnosis of the three groups. The area under the curves (AUCs) of above indicators and combination of four image features except peritoneal carcinomatosis for the differential diagnosis of BeEOTs and BEOTs, BEOTs and MEOTs ranged from 0.74 to 0.85, 0.58 to 0.79, respectively. CONCLUSION: In this study, the characteristics of MRI can provide objective quantitative indicators for the accurate imaging diagnosis of three categories of EOTs and are helpful for clinical decision-making. Among these MRI characteristics, the volume, diameter, and enhancement degrees of the solid portion showed good diagnostic performance.

Correlation Between Clinical Outcomes and Serum CA-125 Levels After Standard Treatment for Epithelial Ovarian Cancer.

BACKGROUND/AIM: To analyze the relationship between clinical outcomes for epithelial ovarian cancer and serum CA-125 levels after chemotherapy in Korean women. PATIENTS AND METHODS: This study included 183 patients who underwent the standard treatment regimen for epithelial ovarian cancer. They were divided into early- (I, II) and advanced-stage (III, IV) groups. Serum CA-125 level after adjuvant chemotherapy completion (post-chemotherapy; PC-CA-125) was measured. Overall survival (OS), progression-free survival (PFS), platinum-free interval (PFI), and platinum resistance were evaluated. RESULTS: In advanced-stage group, OS, PFS, PFI, and platinum resistance were significantly correlated with PC-CA-125. In early-stage group, PFS and platinum resistance differed significantly. Cutoff value for platinum resistance was 10.45 U/ml, 10.40 U/ml, and 15.80 U/ml for study population, early stage, and advanced groups, respectively. Accuracy was 71.1%-77.1%. CONCLUSION: PC-CA-125 is correlated with clinical outcomes in ovarian cancer. Thus, CA-125 can be used to predict platinum resistance in ovarian cancer treatment.

Analysis of serum HE4 levels in various histologic subtypes of epithelial ovarian cancer and other malignant tumors.

BACKGROUND: The measurement of serum HE4 levels has emerged as a sensitive and specific biomarker for epithelial ovarian cancers (EOCs). However, serum levels in women diagnosed with various histologic subtypes of EOC and in women with metastatic non-ovarian primary malignancies have not been widely reported. OBJECTIVE: The goal of this study was to identify how serum HE4 levels vary in women diagnosed with different histologic subtypes of EOC and non-ovarian malignancies. METHODS: Data from six prospective pelvic mass clinical trials was combined and an evaluation of serum HE4 levels in women diagnosed with a malignancy was performed. For all patients, serum was obtained prior to surgery and final pathology, including primary tumor site, histologic subtype, grade and stage, were recorded. The mean, median, standard deviation, maximum, and minimum HE4 levels were determined for each group. RESULTS: A total of 984 patients were included in this study, with the average patient age being 60 years old. There were 230 premenopausal and 754 postmenopausal patients. Serum HE4 levels were elevated (≥70.0 pMol) in 85%of EOCs, 40%of LMP tumors, 21%of non-EOCs (germ cell tumors), 25%of cervical cancers, and 47%of non-gynecologic metastatic cancers. Analysis of histologic subtypes revealed 90%(n = 391) of serous, 85%(n = 73) of endometrioid, 45%(n = 42) of mucinous, 86%(n = 51) of mixed tumors, and 69%(n = 36) of clear cell tumors had elevated serum HE4 levels. CONCLUSIONS: Serum HE4 levels are most often elevated in women with high grade serous and endometrioid EOCs, and though serum elevations are seen more often with advanced stage disease, HE4 is also often elevated in early stage disease and lower grade tumors.

The Prognostic Value of Circulating Tumor DNA in Ovarian Cancer: A Meta-Analysis.

Background: Studies have shown that circulating tumor DNA (ctDNA) indicates a poor prognosis in ovarian cancer. In this study, meta-analysis was used to assess the relationship between ctDNA and the prognosis of patients with epithelial ovarian cancer. Methods: The clinical trials included in this study were obtained via a search of PubMed, the Cochrane Library, the Web of Science and Embase between the period of establishment and March 2020. We selected clinical studies using qualitative or quantitative ctDNA methods to analyse the prognosis of ovarian epithelial cancer, screened the studies according to the determined inclusion and exclusion criteria, and used the modified JADAD score scale and NOS scale for evaluation, with OS (overall survival) and PFS (progression-free survival) as end events. The Cochrane Evaluation Tool was used to evaluate the quality of the randomized controlled trials. Stata 15.0 software was used to combine the effect ratio (hazard ratio, HR) and its 95% confidence interval (CI). In addition, a source analysis of ctDNA specimens, an analysis of ctDNA detection methods and a subgroup and sensitivity analysis of FIGO staging were performed. Results: A total of 8 studies were included in this meta-analysis, and ctDNA was found to be an independent risk factor for patients with epithelial ovarian cancer (OS: HR = 2.36, 95% CI [1.76,3.17], P < .001; PFS: HR = 2.51, 95% CI [1.83,3.45]). Conclusions: The results of our analysis suggested that ctDNA is a potential biomarker that can be used to evaluate the prognosis of patients with ovarian cancer.

Application value of Doppler ultrasound combined with CA125 and CA19.9 in the early diagnosis of epithelial ovarian cancer.

PURPOSE: An early diagnosis is of great significance in improving the survival rate of patients. At present, the application values of different diagnostic methods in ovarian cancer are different, and the clinical diagnosis alone is not ideal. Therefore, this study explored the application value of Doppler ultrasound combined with CA125 and CA19.9 in the early diagnosis of epithelial ovarian cancer. METHODS: A total of 58 patients with ovarian diseases were divided into an observation group (epithelial ovarian cancer group, n=29) and a control group (benign ovarian tumour group, n=29). Doppler ultrasound results and serum CA125 and CA19.9 detection results of the two groups were collected to analyse and compare the application values of ultrasound and different kinds of tumour markers in the early diagnosis of epithelial ovarian cancer. RESULTS: The results of Doppler ultrasound showed that the resistance index of the blood flow in the observation group was lower than that in the control group, and the ultrasound score was higher than that in the control group (p<0.05). The levels of serum tumour markers CA125 and CA19.9 in the observation group were significantly higher than those in the control group (p<0.05). The results of the repeated measurement analysis of variance showed that there were significant differences in the ultrasound score, blood flow resistance index, and CA125 and CA19.9 levels in different stages of ovarian cancer (p<0.05). There was no difference in the ultrasonographic score between stage I and the partum stage, while the stages of menstruation and implantation showed a gradually increasing trend (p<0.05). The blood flow resistance index and CA125 and CA19.9 levels increased gradually with the stage (p<0.05). The sensitivity (93.1%), specificity (96.55%), positive predictive value (96.43%), negative predictive value (93.33%) and diagnosis rate (94.83%) of Doppler ultrasonography combined with CA125 and CA19.9 in the diagnosis of epithelial ovarian cancer were higher than those of the single indicator detection method or the two combined diagnostic detection methods. CONCLUSION: Doppler ultrasound combined with CA125 and CA19.9 has high sensitivity, high specificity and high coincidence rate and can improve the early clinical diagnosis of epithelial ovarian cancer.

SPME-LC/MS-based serum metabolomic phenotyping for distinguishing ovarian cancer histologic subtypes: a pilot study.

Epithelial ovarian cancer (EOC) is the most common cause of death from gynecological cancer. The outcomes of EOC are complicated, as it is often diagnosed late and comprises several heterogenous subtypes. As such, upfront treatment can be highly challenging. Although many significant advances in EOC management have been made over the past several decades, further work must be done to develop early detection tools capable of distinguishing between the various EOC subtypes. In this paper, we present a sophisticated analytical pipeline based on solid-phase microextraction (SPME) and three orthogonal LC/MS acquisition modes that facilitates the comprehensive mapping of a wide range of analytes in serum samples from patients with EOC. PLS-DA multivariate analysis of the metabolomic data was able to provide clear discrimination between all four main EOC subtypes: serous, endometrioid, clear cell, and mucinous carcinomas. The prognostic performance of discriminative metabolites and lipids was confirmed via multivariate receiver operating characteristic (ROC) analysis (AUC value > 88% with 20 features). Further pathway analysis using the top 57 dysregulated metabolic features showed distinct differences in amino acid, lipid, and steroids metabolism among the four EOC subtypes. Thus, metabolomic profiling can serve as a powerful tool for complementing histology in classifying EOC subtypes.

Biomarker-based early detection of epithelial ovarian cancer based on a five-protein signature in patient's plasma - a prospective trial.

BACKGROUND: Trial on five plasma biomarkers (CA125, HE4, OPN, leptin, prolactin) and their possible role in differentiating benign from malignant ovarian tumors. METHODS: In this unicentric prospective trial preoperative blood samples of 43 women with ovarian masses determined for ovarian surgery were analyzed. 25 patients had pathologically confirmed benign, 18 malignant ovarian tumors. Blood plasma was analyzed for CA125, HE4, OPN, leptin, prolactin and MIF by multiplex immunoassay analysis. Each single protein and a logistical regression model including all the listed proteins were tested as preoperative predictive marker for suspect ovarian masses. RESULTS: Plasma CA125 was confirmed as a highly accurate tumor marker in ovarian cancer. HE4, OPN, leptin and prolactin plasma levels differed significantly between benign and malignant ovarian masses. With a logistical regression model a formula including CA125, HE4, OPN, leptin and prolactin was developed to predict malignant ovarian tumors. With a discriminatory AUC of 0.96 it showed to be a highly sensitive and specific diagnostic test for a malignant ovarian tumor. CONCLUSIONS: The calculated formula with the combination of CA125, HE4, OPN, leptin and prolactin plasma levels surpasses each single marker in its diagnostic value to discriminate between benign and malignant ovarian tumors. The formula, applied to our patient population was highly accurate but should be validated in a larger cohort. TRIAL REGISTRATION: Clinical Trials.gov under NCT01763125 , registered Jan. 8, 2013.

Soluble B7-H3 in Ovarian Cancer and Its Predictive Value.

The content of the soluble form of protein of the key point of immunity B7-H3 (sB7-H3) in the blood plasma of 75 patients with epithelial ovarian cancer before treatment was measured by ELISA. It is known that B7-H3 belongs to the immunoglobulin superfamily (B7 molecule family) and is involved in the regulation of the immune response mediated by T cells. The sB7-H3 concentration correlated with the clinical and morphological parameters of ovarian cancer. The content of sB7-H3 was higher at the later stages of the disease, in the presence of ascites, and in patients with poorly differentiated ovarian cancer. It was revealed that increased plasma content of sB7-H3 in patients with epithelial ovarian cancer is associated with unfavorable prognosis of the disease. Therefore, sB7-H3 can be used as a prognostic marker in ovarian cancer patients.

Cell-free DNA is abundant in ascites and represents a liquid biopsy of ovarian cancer.

OBJECTIVE: Malignant ascites is a common clinical feature of ovarian cancer and represents a readily accessible sample of tumour cells and tumour DNA. This study aimed to characterise the cell-free DNA (cfDNA) in ascites in terms of its size profile, stability and cell-free tumour DNA (cftDNA) content. METHODS: Cell spheroids, loose cells and cell-free fluid was collected from ascites from 18 patients with ovarian cancer. cfDNA was isolated and assessed for size by electrophoresis, concentration by fluorometry,cftDNA content by methylation specific qPCR of HOXA9 and IFFO1 promoter regions and by targeted sequencing. Stability was assessed after ascites fluid was stored at 4 °C for 24 and 72 h before fractionating. RESULTS: The concentration of cfDNA in ascites ranged from 6.6 to 300 ng/mL. cfDNA size distribution resembled blood plasma-derived cfDNA, with major peaks corresponding to mono- and di-nucleosome DNA fragments. High molecular weight cfDNA was observed in 7 of 18 patients and appeared to be associated with extracellular vesicles. IFFO1 and HOXA9 methylation was proportionately higher in cfDNA than spheroid- and loose-cell fractions and was not observed in healthy primary cells. Variant allele frequency was highest in cfDNA compared to single cells and spheroids from ascites. Though cancer cell numbers in ascites declined to near zero in recurrent ascites from one patient undertaking chemotherapy, cftDNA could still be sampled. cfDNA size, concentration and tumour content was stable over 72 h. CONCLUSION: cfDNA in ovarian cancer ascites demonstrates inter-patient variability, yet is consistently a rich source of cftDNA, which is a stable substrate. This supports the wider clinical use of ascites in the molecular analysis of ovarian cancer.

CA125 normalization within 60 days as an independent prognostic factor for patients with advanced epithelial ovarian cancer.

BACKGROUND: CA125 level normalization at different chemotherapy cycles has been reported to be a prognosticator in advanced epithelial ovarian cancer. OBJECTIVE: In the present study, we investigated whether the time (in days) to CA125 normalization or nadir during treatment could be used as markers to predict survival. METHODS: Patients with FIGO stage III-IV epithelial ovarian cancer treated with cytoreductive surgery followed by adjuvant chemotherapy between 2008 and 2016 were enrolled in this retrospective study. Clinicopathological characteristics, changes in CA125 level during treatment, and survival outcomes were analyzed. Time-dependent receiver operating characteristic curve analysis was used to determine the optimal cut-off values of the time to normalization and time to nadir of CA125 levels to predict survival. Univariate and multivariate Cox regression analysis were used to examine the impact of each variable on survival. RESULTS: A total of 106 patients were included in the analysis. The optimal cut-off values for the time to normalization and nadir for predicting survival were 60 and 194 days, respectively. In Kaplan-Meier survival analysis, CA125 level normalization ⩽ 60 days and CA125 ⩽ 35 u/mL after the third cycle, and CA125 level ⩽ 10 u/mL after the sixth cycle of chemotherapy were associated with significantly better 5-year progression-free survival (PFS) and overall survival (OS). In multivariate analysis, only CA125 level normalization > 60 days was significantly associated with poor survival outcomes (PFS, HR 2.62 [95% CI: 1.54, 4.45], p= 0.004; OS, HR 2.40 [95% CI: 1.19, 4.81], p= 0.014). CONCLUSIONS: Normalization of CA125 level within 60 days after cytoreductive surgery followed by adjuvant chemotherapy in patients with advanced ovarian epithelial cancer could be used as a marker to predict survival.

Ovarian Cancer Risk in Relation to Blood Cholesterol and Triglycerides.

BACKGROUND: The association between circulating cholesterol and triglyceride levels and ovarian cancer risk remains unclear. METHODS: We prospectively evaluated the association between cholesterol [total, low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C)] and triglycerides and ovarian cancer incidence in a case-control study nested in the Nurses' Health Study (NHS) and NHSII cohorts and a longitudinal analysis in the UK Biobank. RESULTS: A total of 290 epithelial ovarian cancer cases in the NHS/NHSII and 551 cases in UK Biobank were diagnosed after blood collection. We observed a reduced ovarian cancer risk comparing the top to bottom quartile of total cholesterol [meta-analysis relative risk (95% confidence interval): 0.81 (0.65-1.01), P trend 0.06], with no heterogeneity across studies (P heterogeneity = 0.74). Overall, no clear patterns were observed for HDL-C, LDL-C, or triglycerides and ovarian cancer risk. Comparing triglyceride levels at clinically relevant cut-off points (>200 vs. ≤200 mg/dL) for cases diagnosed more than 2 years after blood draw saw a positive relationship with risk [1.57 (1.03-2.42); P heterogeneity = 0.003]. Results were similar by serous/non-serous histotype, menopausal status/hormone use, and body mass index. CONCLUSIONS: Data from two large cohorts in the United States and United Kingdom suggest that total cholesterol levels may be inversely associated with ovarian cancer risk, while triglycerides may be positively associated with risk when assessed at least 2 years before diagnosis, albeit both associations were modest. IMPACT: This analysis of two large prospective studies suggests that circulating lipid levels are not strongly associated with ovarian cancer risk. The positive triglyceride-ovarian cancer association warrants further evaluation.

Wide-Targeted Metabolome Analysis Identifies Potential Biomarkers for Prognosis Prediction of Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is a fatal gynecologic cancer, and its poor prognosis is mainly due to delayed diagnosis. Therefore, biomarker identification and prognosis prediction are crucial in EOC. Altered cell metabolism is a characteristic feature of cancers, and metabolomics reflects an individual's current phenotype. In particular, plasma metabolome analyses can be useful for biomarker identification. In this study, we analyzed 624 metabolites, including uremic toxins (UTx) in plasma derived from 80 patients with EOC using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Compared with the healthy control, we detected 77 significantly increased metabolites and 114 significantly decreased metabolites in EOC patients. Especially, decreased concentrations of lysophosphatidylcholines and phosphatidylcholines and increased concentrations of triglycerides were observed, indicating a metabolic profile characteristic of EOC patients. After calculating the parameters of each metabolic index, we found that higher ratios of kynurenine to tryptophan correlates with worse prognosis in EOC patients. Kynurenine, one of the UTx, can affect the prognosis of EOC. Our results demonstrated that plasma metabolome analysis is useful not only for the diagnosis of EOC, but also for predicting prognosis with the variation of UTx and evaluating response to chemotherapy.

Prolactin and Risk of Epithelial Ovarian Cancer.

BACKGROUND: Prolactin is synthesized in the ovaries and may play a role in ovarian cancer etiology. One prior prospective study observed a suggestive positive association between prolactin levels and risk of ovarian cancer. METHODS: We conducted a pooled case-control study of 703 cases and 864 matched controls nested within five prospective cohorts. We used unconditional logistic regression to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between prolactin and ovarian cancer risk. We examined heterogeneity by menopausal status at blood collection, body mass index (BMI), age, and histotype. RESULTS: Among women with known menopausal status, we observed a positive trend in the association between prolactin and ovarian cancer risk (P trend = 0.045; OR, quartile 4 vs. 1 = 1.34; 95% CI = 0.97-1.85), but no significant association was observed for premenopausal or postmenopausal women individually (corresponding OR = 1.38; 95% CI = 0.74-2.58; P trend = 0.32 and OR = 1.41; 95% CI = 0.93-2.13; P trend = 0.08, respectively; P heterogeneity = 0.91). In stratified analyses, we observed a positive association between prolactin and risk for women with BMI ≥ 25 kg/m2, but not BMI < 25 kg/m2 (corresponding OR = 2.68; 95% CI = 1.56-4.59; P trend < 0.01 and OR = 0.90; 95% CI = 0.58-1.40; P trend = 0.98, respectively; P heterogeneity < 0.01). Associations did not vary by age, postmenopausal hormone therapy use, histotype, or time between blood draw and diagnosis. CONCLUSIONS: We found a trend between higher prolactin levels and increased ovarian cancer risk, especially among women with a BMI ≥ 25 kg/m2. IMPACT: This work supports a previous study linking higher prolactin with ovarian carcinogenesis in a high adiposity setting. Future work is needed to understand the mechanism underlying this association.

Clinical significance of circulating tumor cell related markers in patients with epithelial ovarian cancer before and after adjuvant chemotherapy.

Circulating tumor cells (CTCs) have recently been considered as new prognostic and diagnostic markers for various human cancers; however, their significance in epithelial ovarian cancer (EOC) remains to be elucidated. In this study, using quantitative real-time PCR, we evaluated the expression of EPCAM, MUC1, CEA, HE4 and CA125 mRNAs, as putative markers of CTCs, in the blood of 51 EOC patients before and/or after adjuvant chemotherapy. Our results demonstrated that, before chemotherapy, the expression of EPCAM, MUC1, CEA and HE4 mRNAs were correlated to each other. CEA expression was correlated with tumor stage (r = 0.594, p = 0.000) before chemotherapy, whereas its expression after chemotherapy was correlated with serum levels of CA125 antigen (r = 0.658, p = 0.000). HE4 mRNA showed the highest sensitivity both before and after chemotherapy (82.98% and 85.19%, respectively) and the persistence of this marker after chemotherapy was associated with advanced disease stage. The expression of CA125 mRNA had negative correlation with the other markers and with tumor stage and therapy response (evaluated by the measurement of serum CA125 antigen). Collectively, our results indicated a better clinical significance of tumor-specific markers (CEA and HE4 mRNAs) compared to epithelial-specific markers (EPCAM and MUC1 mRNAs).

Review of biomarker systems as an alternative for early diagnosis of ovarian carcinoma.

Early diagnosis of ovarian carcinoma is bound to boost the long-term endurance rate of the patients. Most ovarian tumors happen post menopause when the ovaries have no vital operation and therefore irregular ovarian role causes no signs. According to Muinao T. et al. (Heliyon. 5(12):e02826, 2019), if we consider the frequency of ovarian carcinoma to be moderate, a screening technique must accomplish a base specificity of 99.6% and sensitivity of over 75%. The classification and approval of early diagnostic biomarkers explicit to ovarian carcinoma are essentially required. Prevailing methods for early diagnosis of ovarian carcinoma incorporate TVS, biological marker examination, or a blend of the two or other. In recent years, it has been revealed that a combination of at least two biomarkers has beaten single biomarkers in measures for early diagnosis of the illness. In the present document, we survey the ongoing exploration of innovative characteristic methodologies and possible panels of carcinoma biological markers for the early diagnosis of ovarian carcinoma and discuss biomarkers as the plausible apparatus for model improvement and other progressed approaches as an effective alternative to the prevailing methods for early diagnosis of this dreadful disease to evade bogus analysis and inordinate expense.

Epithelial ovarian cancer and the use of circulating tumor DNA: A systematic review.

OBJECTIVE: One way to improve the survival rate of epithelial Ovarian Cancer (EOC) is by identifying effective biomarkers useful at different stages and time points of the disease. A potential biomarker is circulating tumor DNA (ctDNA) in plasma or serum. In this systematic review, we provide an overview of applications of ctDNA in EOC to discuss the direction of future research in this field. METHODS: We performed a systematic search in Pubmed, Embase, and Scopus to identify relevant clinical studies eligible for inclusion. Furthermore, the references in the identified studies and relevant reviews were assessed to identify additional studies. The PRISMA guideline was employed to perform the systematic review, and data from the studies were extracted using piloted data extraction forms. RESULTS: A total of 36 observational studies were included. The concordance between tumor and ctDNA was assessed in 19 studies, early diagnosis in 1, diagnosis in 23, monitoring of treatment response in 7, detection of reversion mutations in 3, prognosis in 9, but no studies assessed early detection of recurrence. Data from the studies were reported descriptively. The studies had a large variation in the methods used for ctDNA analysis and limited sample sizes of 10-126 patients. Overall, the studies show that ctDNA is a potential biomarker for EOC useful in several settings during assessment and treatment of these patients. CONCLUSIONS: Although the identified studies are limited in number and their methods for ctDNA analysis vary, it is clear that ctDNA as a biomarker for EOC is promising for several applications in diagnostics, monitoring of treatment response, and prognostics. However, more studies are needed to establish the ideal methods and settings for the clinical use of ctDNA in EOC.