Diagnosis Of Epithelial Ovarian Cancer Research Articles

Diagnosing and staging epithelial ovarian cancer by serum glycoproteomic profiling.

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. 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. 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. 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.

The evaluation of miR-1181 and miR-4314 as serum microRNA biomarkers for epithelial ovarian cancer diagnosis and prognosis.

Epithelial ovarian cancer (EOC) is the most ominous tumor of gynecological cancers due to its poor early detection rate and unfavorable prognosis. To date, there is no reliable screening method for the diagnosis of ovarian cancer at an early stage. MiRNAs are small non-coding RNA molecules, and their main function is to regulate gene expression. The present study compared the serum miR-1181 and miR-4314 levels in patients with EOC and healthy controls to measure the diagnostic and prognostic value as candidate biomarkers. We collected serum samples from a total of 135 participants (69 patients with EOC and 66 healthy controls). Relative expressions of miR-1181 and miR-4314 were measured by quantitative real-time polymerase chain reaction assay (qPCR). The present study revealed that both serum miR-1181 and miR-4314 levels in patients with EOC were significantly increased compared to healthy controls for each marker. In addition, there was a significant relationship between miR-1181 and miR-4314 overexpressions and the stage and prognosis of the disease. Finally, patients with high expression levels of miR-1181 and miR-4314 had significantly shorter survival rates than those with low expression levels. The current study proposed that serum miR-1181 and miR-4314 could discriminate the EOC patients from healthy controls. In addition, both miR-1181 and miR-4314 may be predictive biomarkers for ovarian cancer prognosis. Further studies are needed to confirm the findings of the present study.

Abstract LB381: Plasma microbiota as novel biomarkers of early epithelial ovarian cancer detection

Abstract Background: Ovarian cancer accounts for 2% of all female cancers in the United States yet it is the 5th leading cancer death among women. Advanced epithelial ovarian cancer (EOC) is associated with an overall survival rate of 30% but can be cured in up to 90% of cases if diagnosed early when the disease is still limited to the ovaries and fallopian tubes. While there is no effective screening method for EOC, developing novel and minimally invasive clinical tests is paramount to identify women with early disease as well as those who are at increased risk. Plasma-based microbiota signatures specific to EOC could become leading biomarkers of early disease in the field that complement existing clinical tools. Methods: We utilized an established institutional biobank to access 180 biobanked plasma samples from: (1) women with EOC; (2) women with non-EOC solid tumors; (3) women undergoing gynecologic-related procedures and non-EOC surgeries; and (4) healthy controls. Batch 1 included 96 plasma samples (n=24 per group) and Batch 2 included 84 samples (n=19 per group and 8 repeat EOC samples). Microbial profiles of plasma specimens were assessed using an amplicon-based sequencing method that targets the 16S rRNA gene in the bacterial genome to study bacterial phylogeny and taxonomy in diseased and healthy women. A stringent bioinformatic pipeline was applied to filter out suspicious bacterial contaminants at the genus level. Bacterial decontamination procedures in the pipeline included evaluating repeat plasma samples of EOC cases and sampling nucleic acid isolation kit reagents to serve as negative controls (only in Batch 2) . Differential abundances of the plasma microbiota among the groups were assessed using analysis of compositions of microbiomes (ANCOM) as implemented in R software package ANCOM-BC. Results: The 16S rRNA gene sequencing identified, classified, and quantified 564 bacterial genera in the circulation of women diagnosed with EOC, non-EOC solid tumors, benign gynecologic conditions, and healthy controls. Bioinformatic decontamination analysis removed bacteria: (1) with differing bacterial abundances between batches; (2) with higher bacteria in negative controls; (3) with differing bacterial abundances in repeat samples; and (4) known as contaminants in the literature that resulted in the removal of 225 high-risk bacterial contaminants. A total of 339 high quality bacteria remained for evaluation. Because we did not collect negative controls in Batch 1, only Batch 2 plasma samples (n=84; 27 in EOC group; 19 in each other group) were included in the final analysis. Women with EOC, which were primarily of the high-grade serous ovarian carcinoma histologic subtype had significantly distinct differential abundances of genera Brevibacterium (p <0.001), Chloronema (p <0.001), Facklamia (p <0.001), Zymomonas (p <0.001), and Sutterella (p <0.001) when compared to women with non-EOC solid tumors, benign gynecologic conditions, and healthy controls. Conclusions: These findings suggest that plasma EOC-associated bacteria could be exploited in the development of a microbial-based blood test for the diagnosis and early detection of EOC in routine practice settings. Citation Format: Diane E. Mahoney, Prabhakar Chalise, Dong Pei, Rachel Griffard, Trisha Home, Harsh Pathak, Shahid Umar, Andrew K. Godwin. Plasma microbiota as novel biomarkers of early epithelial ovarian cancer detection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB381.

Epithelial Ovarian Cancer: The Importance of Early Diagnosis and Individualized Treatment with Combination Chemotherapy and Targeted Therapy

Epithelial ovarian cancer is a malignant neoplasm that represents the majority of ovarian cancer cases. It is characterized by aggressiveness, often late diagnosis and therapeutic challenges. Early diagnosis is crucial to improving patients' survival rates and quality of life. Individualized treatment, combining chemotherapy and targeted therapy, has been a promising approach to optimize therapeutic results and minimize adverse effects. Objective: to analyze and synthesize the available evidence on the importance of early diagnosis and individualized treatment with combined chemotherapy and targeted therapy in epithelial ovarian cancer. Methodology: Using the PRISMA checklist, this review was conducted based on articles published in the last 10 years. The databases used were: PubMed, Scielo, Web of Science. The descriptors: "epithelial ovarian cancer", "early diagnosis", "individualized treatment", "combined chemotherapy", "targeted therapy". Inclusion criteria: original studies in humans, published in English or Portuguese, addressing the early diagnosis and/or individualized treatment of epithelial ovarian cancer. Exclusion criteria: animal studies, systematic reviews, studies with non-representative samples. Results: The results of this review highlight the importance of early diagnosis through imaging techniques and tumor markers. Furthermore, they highlight the effectiveness of combination chemotherapy, especially regimens containing platinum and taxanes, together with targeted therapy, such as PARP inhibitors, in improving response rates and survival in patients with epithelial ovarian cancer. Conclusion: Early diagnosis and individualized treatment with combination chemotherapy and targeted therapy play a key role in the management of epithelial ovarian cancer. This multifaceted approach can significantly improve patients' clinical outcomes and quality of life, highlighting the importance of personalized therapeutic strategies in this challenging clinical context.

Prediagnostic use of menopausal hormone therapy and long-term survival of localized epithelial ovarian cancer: The Extreme study.

Use of menopausal hormone therapy (MHT) prior to an epithelial ovarian cancer (EOC) diagnosis has been suggested to be associated with improved survival. In a recent nationwide cohort study, we found that prediagnostic long-term MHT use, especially estrogen therapy (ET), was associated with improved long-term survival in women with nonlocalized EOC. Our aim was to investigate the influence of prediagnostic MHT use on long-term survival among women with localized EOC in the same nationwide study. Our study cohort comprised all women aged 50 years or older with an EOC diagnosis in Denmark 2000-2014 (n = 2097) identified from the Extreme study. We collected information on usage of systemic ET and estrogen plus progestin therapy (EPT) from the Danish National Prescription Registry. By using pseudo-values, 5- and 10-year absolute and relative survival probabilities were estimated with 95% confidence intervals (CIs) while adjusting for histology, comorbidity, and income. Relative survival probabilities >1 indicate better survival. The 5-year absolute survival probabilities were 61% and 56%, respectively, among women who were nonusers and users of prediagnostic MHT, whereas these numbers were 46% and 41%, respectively, regarding 10-year survival. Use of MHT was not significantly associated with an improved 5- or 10-year survival in women with localized EOC (5-year relative survival probability = 0.95, 95% CI: 0.89-1.02; 10-year relative survival probability = 0.92, 95% CI: 0.84-1.02). Similar findings were seen for systemic ET or EPT use. Our findings do not suggest a positive benefit from prediagnostic MHT use on long-term survival of localized EOC.

Abstract A056: Development and application of an epithelial ovarian cancer-specific line of therapy algorithm using real-world data

Abstract Introduction. Characterizing lines of therapy (LoTs) helps researchers describe the epithelial ovarian cancer (EOC) patient treatment journey, but they are not routinely captured in real-world data. Algorithms must therefore be developed to transform individual treatment data into summary LoTs. Special considerations must be made for EOC as maintenance (MTx) therapy, which includes poly ADP ribose polymerase inhibitors (PARPi) and/or bevacizumab, may be given following treatment (Tx) lines. We developed an EOC-specific LoT algorithm and evaluated its performance using real-world data. Methods. Patients were sampled from the Syapse Learning Health Network, a database of cancer patients treated in large community health systems across 25 states in the US and were eligible for inclusion if they were diagnosed with EOC between 01/01/2015 and 09/30/2022 (index date) and had manually curated systemic therapy data. All patients were followed through 12/31/2022. Assignment of Tx and MTx lines and regimens and allowable treatment gaps were based on national treatment guidelines and typical disease course. To distinguish between Tx and MTx lines, all eligible patients who received systemic therapy following the initial diagnosis of EOC were assigned first-line (1L) Tx, and each subsequent LoT was classified as a Tx or MTx line depending on the therapies in the present LoT and one immediately preceding it. Therapies could be added or switched within a LoT, and assigned regimens distinguished between therapies given in combination from switch therapies. A shorter treatment gap was used to identify later LoTs to account for more rapid disease progression. Unexpected regimens were flagged for further evaluation. A subset of patients with advanced stage, non-mucinous EOC who received 1L platinum-based chemotherapy were manually reviewed by a medical oncologist to identify patients who received 1L MTx. Results. There were 2,275 eligible EOC patients. 415 patients with missing, incomplete, or invalid therapy dates were excluded, leaving 1,860 patients in the LoT analysis. Median follow-up was 23 months (IQR, 13-41 months). Nearly half (48%) of the patients received only one LoT; 15% of patients received 3 or more LoTs. Out of all patients, 15% received 1L MTx without any subsequent treatment. The top 1L Tx regimens were platinum and taxane combination, platinum and taxane plus bevacizumab, and platinum alone (73%, 16%, and 2% of patients who received 1L Tx, respectively). The top 1L MTx regimen was PARPi alone, followed by bevacizumab alone and bevacizumab plus PARPi (57%, 35%, and 8% of patients who received 1L MTx, respectively). 1,355 (74%) patients were identified for expert review. Among these, concordance in 1L MTx determination between expert review and the algorithm was 98%. Conclusion. The EOC-specific LoT algorithm performed well: line and regimen distributions aligned with real-world practice and expert clinical review. Researchers may wish to utilize this algorithm for real-world studies of ovarian cancer. Citation Format: Connor Sweetnam, Tirza Areli Calderón Boyle, Sara Burns, Jessica Perhanidis, Matthew Rioth, Rayna K Matsuno. Development and application of an epithelial ovarian cancer-specific line of therapy algorithm using real-world data [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A056.

Diagnostic value of plasma-derived exosomal miR-223 for epithelial ovarian cancer

ObjectivesTo evaluate the diagnostic value of plasma exosomal miR-223 and its combination with CA125 for the diagnosis of early-stage epithelial ovarian cancer (EOC).Patients and methodsExosomes derived from the plasma of 78 EOC patients, 40 patients with epithelial benign ovarian tumors, and 52 healthy participants were isolated using the ultracentrifugation method and identified by transmission electron microscopy (TEM) and western blot.ResultsThe expression of exosomal miR-223 was significantly upregulated in the plasma of EOC patients compared to that in healthy subjects and patients with benign diseases. The combination of exosomal miR-223 and CA125 from plasma had an equivalent area under the ROC curve (AUC) to CA125 alone for discriminating between EOC and non-EOC cases, including healthy subjects and benign ovarian tumors. However, the AUC value of the combination was 0.944 (95% CI: 0.899–0.990) for differentially diagnosing early-stage EOC from healthy subjects, slightly higher than that of CA125 alone (0.928, 95% CI: 0.875–0.981), with a sensitivity and specificity of 0.9784 and 0.885, respectively.ConclusionOur data suggest that plasma exosomal miR-223 can be used as a complement to CA125 to increase the diagnostic power for differentiating early-stage EOC from healthy subjects.

Evaluation of the Cutoff Point and Diagnostic Value of the Neutrophil-to-Lymphocyte Ratio in Predicting Ovarian Cancer Compared to Pathological Findings.

This research aims to establish a neutrophil-to-lymphocyte ratio (NLR) threshold and evaluate its diagnostic accuracy compared to pathological criteria for diagnosing Epithelial Ovarian Cancer (EOC). We conducted a cross-sectional study at Imam Hossein Hospital involving 204 women aged 18 and older with confirmed ovarian mass based on pathology. We recorded clinical, pathological, and preoperative blood count data, including neutrophil-to-lymphocyte ratio (NLR). Patients were categorized into malignant and benign ovarian mass groups based on postoperative pathology. The power of NLR to diagnosis of EOC was evaluated using ROC curve. At total, 204 patients (Benign 75.5% vs. Malignant 24.5%) were included in the analysis with mean age of 54.26 ±12.04 yrs in malignant and 46.31±13.21 in benign. In all cases, the proportion of patients with the following tumor markers HE4 (>140 Pm), CA 125 (> 35U/Ml) and CEA (>5 ng/Ml) were 52.45%, 41.67% and 3.43%, respectively, and proportion of abnormal tumor markers was statistically higher in malignant group compared to benign mass (p <0.05). Odds of having higher NLR levels in the malignancy group was higher than benign group (e.g., OR of 4.45 for NLR in quartile 4 vs. quartile 1). According to model selection criteria, the full model with including NLR level and age, BMI and tumor markers has best performance for diagnosis of malignancy (AUC =0.87). High NLR in combination with tumor markers including CA125, HE4 and CEA were associated with malignancy in patients with ovarian mass. More attention and further examinations should be devoted for patients with ovarian mass having high NLR and abnormal tumor markers levels to detect the probable malignancy as soon as possible.

Association between diet quality and ovarian cancer risk and survival.

Research on diet quality and ovarian cancer is limited. We examined the association between diet quality and ovarian cancer risk and survival in a large prospective cohort. We utilized data from women in the prospective NIH-AARP Diet and Health Study enrolled from 1995-1996 and were 50-71 years old at baseline with follow-up through 12/31/2017. Participants completed a 124-item Food Frequency Questionnaire at baseline and diet quality was assessed via the Healthy Eating Index-2015 (HEI-2015), the alternate Mediterranean diet score (aMED), and the Dietary Approaches to Stop Hypertension score (DASH). Primary outcomes were first primary epithelial ovarian cancer diagnosis from cancer registry data, and among those diagnosed with ovarian cancer all-cause mortality. We used a semi-Markov multi-state model with Cox proportional hazards regression to account for semi-competing events. Among 150,643 participants with a median follow-up time of 20.5 years, 1,107 individuals were diagnosed with a first primary epithelial ovarian cancer. There was no evidence of an association between diet quality and ovarian cancer risk. Among those diagnosed with epithelial ovarian cancer, 893 deaths occurred with a median survival of 2.5 years. Better pre-diagnosis diet quality, according to the HEI-2015 (Quintile 5 vs Quintile 1 HR = 0.75 [0.60-0.93]) and aMED (Quintile 5 vs Quintile 1: HR = 0.68, [0.53-0.87]) was associated with lower all-cause mortality. There was no evidence of an association between DASH and all-cause mortality. Better pre-diagnosis diet quality was associated with lower all-cause mortality after ovarian cancer diagnosis, but was not associated with ovarian cancer risk.

Correlation between pre-operative platelets count and serum cancer antigen-125 level in epithelial ovarian carcer

Cancer antigen 125 (Ca-125) is currently used as an adjunct to ovarian cancer diagnosis, prognosis, and monitoring. Platelet (PLT) count and Ca-125 levels are both prognostic markers in ovarian cancer that are linked to inflammation and immune evasion.To determine the relationship between pre-operative platelet count and serum Ca-125 level, and their diagnostic accuracy for the prediction of stage IV epithelial ovarian cancer.The study included forty-two women with histologic diagnosis of epithelial ovarian cancer managed at the University of Port Harcourt Teaching Hospital between January 1, 2016, and December 31, 2020. Following informed consent, a data collection form was used to obtain socio-demographic and clinical characteristics. Pretreatment levels of Cancer Antigen 125 (Ca-125) and Platelets count (PLT) were determined from blood samples. The Spearman correlation coefficient was used to determine the relationship between PLT and Ca-125, and the Receiver Operating Characteristic (ROC) curve analysis was used to assess the predictive accuracy of PLT count alone and PLT-Ca-125. The sample median platelet count was 308 (307) x 10/L and median Ca-125 was 286µ/ml (397). Pre-operative platelets count was significantly associated with Ca-125 (rho= 0.28 p-value = 0.03). Ca-125 had a statistically significant relationship with ovarian cancer histology (X2:19.522; p-value 0.001). PLT-Ca-125 (0.51) and PLT only (0.29) had a statistically significant positive correlation with ovarian cancer stage (p 0.001). Since it had an area under the curve (AUC) greater than 0.7, PLT-Ca-125 can be used as a predictive model to correctly stage patients with epithelial ovarian cancer. Ca-125 level (z:-2.24; p-value = 0.025) was significantly associated with thrombocytosis in ovarian cancer patients.Platelet count and Ca-125 levels do correlate in blood samples taken from ovarian cancer patients prior to treatment. Furthermore, PLT-Ca-125 levels could be used to predict advanced stage disease.

HE4 and CA-125 kinetics to predict outcome in patients with recurrent epithelial ovarian carcinoma: the META4 clinical trial.

HE4 and CA-125 are used for epithelial ovarian cancer (EOC) screening, diagnosis, and follow-up. Our objective was to study HE4 and CA-125 kinetics in patients treated for recurrent EOC. Serum samples were prospectively collected before the first chemotherapy cycle and every 3 months until disease progression. Data from 89/101 patients could be analyzed. At baseline, the median CA-125 and HE4 concentrations were 210 IU/L (7-10,310) and 184 pM (31-4,836). Among the 12 patients (13%) with normal CA-125 (<35 IU/L) concentration, eight had HE4 concentration ≥75 pM, and among the 16 patients with normal HE4 concentration (18%), 12 had increased CA-125 concentration. The median nadir concentrations were 31 IU/L (3-8,744) for CA-125 and 75 pM (20-4,836) for HE4. The median times to nadir were 14 (0-130) weeks for CA-125 and 12 (0-52) weeks for HE4. In multivariate analysis, CA-125 and HE4 nadir concentrations (<35 IU/L, HR 0.35, 95% CI: 0.17-0.72 and<75 pM, HR 0.40, 95% CI: 0.20-0.79) and time to CA-125 and HE4 nadir (>14 weeks, HR 0.37, 95% CI: 0.20-0.70 and >12 weeks, HR 0.43, 95% CI: 0.23-0.83) were prognostic factors of progression-free survival. More investigations on HE4 kinetics could help to better monitor patients with CA-125 concentration within normal values.

Drug-Resistant Epithelial Ovarian Cancer: Current and Future Perspectives.

Epithelial ovarian cancer (EOC) is a complex disease with diverse histological subtypes, which, based on the aggressiveness and course of disease progression, have recently been broadly grouped into type I (low-grade serous, endometrioid, clear cell, and mucinous) and type II (high-grade serous, high-grade endometrioid, and undifferentiated carcinomas) categories. Despite substantial differences in pathogenesis, genetics, prognosis, and treatment response, clinical diagnosis and management of EOC remain similar across the subtypes. Debulking surgery combined with platinum-taxol-based chemotherapy serves as the initial treatment for High Grade Serous Ovarian Carcinoma (HGSOC), the most prevalent one, and for other subtypes, but most patients exhibit intrinsic or acquired resistance and recur in short duration. Targeted therapies, such as anti-angiogenics (e.g., bevacizumab) and PARP inhibitors (for BRCA-mutated cancers), offer some success, but therapy resistance, through various mechanisms, poses a significant challenge. This comprehensive chapter delves into emerging strategies to address these challenges, highlighting factors like aberrant miRNAs, metabolism, apoptosis evasion, cancer stem cells, and autophagy, which play pivotal roles in mediating resistance and disease relapse in EOC. Beyond standard treatments, the focus of this study extends to alternate targeted agents, including immunotherapies like checkpoint inhibitors, CAR T cells, and vaccines, as well as inhibitors targeting key oncogenic pathways in EOC. Additionally, this chapter covers disease classification, diagnosis, resistance pathways, standard treatments, and clinical data on various emerging approaches, and advocates for a nuanced and personalized approach tailored to individual subtypes and resistance mechanisms, aiming to enhance therapeutic outcomes across the spectrum of EOC subtypes.

The diagnostic value of systemic inflammatory response markers as predictors of epithelial ovarian cancer

Background: Early detection of ovarian neoplasms confers a better outcome and prognosis for patients. Although newer diagnostic modalities have been recently developed, the availability and accessibility of complete blood count parameters make it a convenient and cost-effective marker for malignancy. Objectives were to evaluate the diagnostic accuracy of pretreatment neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in patients with late-stage epithelial ovarian malignancy at the University of Port Harcourt Teaching Hospital. Methods: A prospective analysis of fifty-seven women with histologic diagnosis of epithelial ovarian cancer who were managed at the University of Port Harcourt Teaching Hospital between January 1, 2018, and December 31, 2022, was conducted. A data collection form was used to obtain socio-demographic and clinico-pathological characteristics from the patients after informed consent was obtained. Pretreatment levels of NLR and PLR were determined from complete blood count. The Receiver Operating Characteristic (ROC) curve analysis was used to assess the predictive accuracy of the haematological parameters for late-stage epithelial ovarian cancer. Results: Higher values of NLR and PLR were significantly associated with the stage of ovarian cancer (p=0.001). The optimal cut-off points based on ROC curve analyses for NLR and PLR were found to be 2.6 (AUC=0.61, p&gt;0.05), and 155.8 (AUC=0.62, p&gt;0.05) respectively. However, none of the haematological parameters could be used as predictive markers for advanced-stage ovarian cancer in this study. Conclusions: Pretreatment NLR and PLR cannot be used as a stand-alone predictor of advanced ovarian cancer, and should be correlated with other clinical, laboratory and radiologic parameters.

Simultaneous detection of CA-125 and mesothelin by gold nanoparticles in surface plasmon resonance

The early-stage diagnosis and monitoring of disease evolution is still one of the most challenging tasks in the field of cancer research. Several research have been driven toward the discovery of new cancer biomarkers as well as to the development of biosensors able to detect these biomarkers with high specificity and sensitivity. Many types of cancer have been detected at an advanced stage and, in particular, epithelial ovarian cancer (EOC) has a high incidence of diagnosis in the metastatic stage. This cancer is considered as the most aggressive type of gynecological cancer with a 5-year survival and until now, no specific biomarkers have been identified. Nevertheless, some studies have indicated that mesothelin, a protein overexpressed by tumour cells in the ovary, interacts with the CA-125 biomarker present in the blood system accelerating the metastatic process. Therefore, the simultaneous presence of CA-125 and mesothelin in the blood during the evolution of EOC could be used to diagnose this disease before the metastasis. Therefore, with this motivation, this work aimed at the development of a biosensor capable of simultaneously detecting mesothelin and CA-125 at low concentrations. A biosensor based on the surface plasmon resonance imaging (SPRi) technique was developed and gold nanoparticles (AuNPs) were used in order to enhance the sensitivity. The study analysed successive injections of the biomarkers CA-125 and mesothelin, both in solution (analytical range of 9–120 nM). The limits of detection were obtained for CA-125 and mesothelin, being of 3.03 nM and 13.62 nM, respectively. The biosensor detected mesothelin at a concentration close to the cutoff point for EOC (3 nM) and was able to detect the biomarker CA-125 at 9 nM. Furthermore, the biosensor interacted preferentially and simultaneously with the biomarkers CA-125 and mesothelin incubated in fetal bovine serum. Finally, the use of AuNPs increased the sensor signal for CA-125 detection compared to its direct detection and showed greater selectivity for both biomarkers. Therefore, the biosensor has important characteristics that allow testing with real samples. In a future project, it could be applied in the research of diagnosis and prognosis of EOC.

Real-world (RW) use of niraparib (Nir) monotherapy (mono) as first-line (1L) switch maintenance (1LSM) therapy following chemotherapy (CT) plus bevacizumab (bev) induction treatment in patients (pts) with epithelial ovarian cancer (EOC) in the SW1TCH study.

536 Background: In the RW CHAR1ZMA study, 414 pts with EOC treated with 1L platinum-based CT (pbCT) and receiving 1L maintenance (1LM) nir mono had a median time to next treatment (TTNT) from end of 1L, a proxy for RW progression-free survival, of 13.3 mo (95% CI, 12.0–15.8 mo).1 Limited data exist on RW outcomes in pts with EOC who receive nir mono as 1LSM after 1L pbCT + bev treatment. The SW1TCH study describes nir mono use and outcomes as 1LSM therapy after 1L pbCT + bev treatment in a US RW setting. Methods: Using the nationwide Flatiron Health electronic health record–derived deidentified database, this retrospective observational study included pts ≥18 y of age at initial EOC diagnosis who received 1L pbCT + bev treatment followed by nir 1LM mono, initiated between Jan 1, 2017, and Sep 2, 2022. The index date was the initiation of nir 1LM. Pts were followed until the earliest of date of death, last activity, or end of study (Nov 30, 2022). Time to treatment discontinuation (TTD) and TTNT were estimated with Kaplan-Meier methods. Results: Of 93 pts selected, median age at index was 67 y (IQR, 60–72 y). Most pts had an Eastern Cooperative Oncology Group performance score of 0–1 (75.3%) and stage III/IV disease at diagnosis (89.2%). Overall, 86.0% of pts had BRCA wild-type EOC. 19.4% and 22.6% of pts had evidence of homologous recombination (HR)-deficient and HR-proficient EOC, respectively, whereas HR deficiency status was unknown for 58.1%. Median duration of 1L therapy was 4.8 mo (IQR, 3.6–6.0 mo), and median time from end of 1L pbCT to start of 1LM was 1.2 mo (IQR, 0.8–1.8 mo). Reasons for nir discontinuation are shown in the Table. Median TTD from index was 9.3 mo (95% CI, 6.0–11.3 mo). Median TTNT from end of 1L was 12.9 mo (95% CI, 11.5–19.0 mo). Conclusions: Observed results are consistent with CHAR1ZMA,1 suggesting the RW benefit of nir mono in 1LM regardless of bev use with1L pbCT. This RW study demonstrates that nir mono as 1LSM therapy is a viable treatment option for pts with advanced EOC.

Exosomes released from PD-L1+ tumor associated macrophages promote peritoneal metastasis of epithelial ovarian cancer by up-regulating T cell lipid metabolism

Epithelial ovarian cancer (EOC) tends to metastasize to the peritoneum, and the prognosis of patients is poor. In the peritoneum of patients with EOC, TAMs (tumor associated macrophages) regulate the imbalance of T cell ratio and promote the progression and metastasis of EOC. However, the mechanism of peritoneal metastasis in EOC patients remains unclear. Here, we confirmed that the percentages of PD-L1+ TAMs in EOC tissues increased significantly, and TAMs-derived PD-L1+ exosomes affected the transcription factor PPARα to up-regulate the expression of CPT1A in CD8+ T cells, promote fatty acid oxidation, and increase reactive oxygen species to cause cell damage. The apoptosis of CD8+ T cells was increased, and the expressions of their exhaustion markers LAG3, TIM-3, and PD-1 were also up-regulated. TAMs affect T cell function through lipid metabolism, leading to peritoneal immune imbalance and promoting peritoneal metastasis of EOC. This study reveals the mechanism by which TAMs in the peritoneal microenvironment regulate T cell lipid metabolism through exosome delivery of PD-L1, and the effect of lipid metabolism on T cell function, reveals the molecular mechanism of tumor immune microenvironment affecting EOC metastasis, and further explores related pathways whether molecular blockade can be used as a means to intervene in disease progression is expected to establish a new strategy for the diagnosis and treatment of EOC.

Purification of Circulating Tumor Cells Based on Multiantibody-Modified Magnetic Nanoparticles and Molecular Analysis toward Epithelial Ovarian Cancer Detection.

Circulating tumor cells (CTCs) are valuable circulating biomarkers of cancer, which carry primary tumor information and may provide real-time assessment of tumor status as well as treatment response in cancer patients. Herein, we developed a novel assay for accurate diagnosis and dynamic monitoring of epithelial ovarian cancer (EOC) using CTC RNA analysis. Multiantibody-modified magnetic nanoparticles were prepared for purification of EOC CTCs from whole blood samples of clinical patients. Subsequently, nine EOC-specific mRNAs of purified CTCs were quantified using droplet digital PCR. The EOC CTC Score was generated using a multivariate logistic regression model for each sample based on the transcripts of the nine genes. This assay exhibited a distinguishing diagnostic performance for the detection of EOC (n = 17) from benign ovarian tumors (n = 30), with an area under the receiver operating characteristic curve (AUC) of 0.96 (95% CI = 0.91-1.00). Moreover, dynamic changes of the EOC CTC Score were observed in patients undergoing treatment, demonstrating the potential of the assay for monitoring EOC. In conclusion, we present an accurate assay for the diagnosis and monitoring of EOC via CTC RNA analysis, and the results suggest that it may provide a promising solution for the detection and treatment response assessment of EOC.

Impact of Sepsis on the Oncologic Outcomes of Advanced Epithelial Ovarian Cancer Patients: A Multicenter Observational Study.

The sepsis-induced inflammatory response may potentially affect malignant cells. Recently, a case of spontaneous regression of a histologically confirmed International Federation of Gynecology and Obstetrics (FIGO) stage IIIC epithelial ovarian cancer (EOC) following sepsis was reported. The aim of our study was to assess the impact of sepsis on the oncologic outcomes of advanced-stage EOC patients. Gynecologic oncologic patients admitted to the Intensive Care Unit of three oncologic centers between 2006 and 2019 were identified and patients who experienced sepsis following advanced-stage EOC diagnosis were selected. Survival outcomes were compared with advanced-stage EOC patients from the Netherlands Cancer Registry (NCR). To correct for case-mix differences, propensity score matching using 1:3 nearest neighbor matching was conducted after which survival analyses were repeated. A total of 18 of 215 patients with advanced-stage EOC experienced sepsis. Sepsis patients had similar distributions of patient, tumor, and treatment characteristics to 3988 patients from the NCR cohort. A total of 3 of 18 patients died from the complications of sepsis. While the remaining patients initially responded to treatment, 14/15 patients relapsed. The median (IQR) overall survival was 31 (24-44) and 35 (20-60) months for the sepsis and unmatched NCR cohort (p = 0.56), respectively. The median (IQR) progression-free survival was 16 (11-21) and 16 (11-27) months (p = 0.90), respectively. Survival outcomes did not differ following propensity matching (overall survival of 31 (24-44) vs. 36 (20-56) months, p = 0.40; progression-free survival of 16 (11-21) and 16 (12-21) months, p = 0.72). In this observational study, the occurrence of sepsis did not affect the oncologic and survival outcomes of advanced-stage EOC patients.

Serum levels of tumor markers and their clinical significance in epithelial ovarian cancer.

Tumor markers have been widely used clinically. Detection of serum CA125 is one of the commonly used clinical methods for early screening and early diagnosis of epithelial ovarian cancer, but it is difficult to diagnose epithelial ovarian cancer with a single specific tumor marker. In this study, the combinatorial tumor marker detection method was used to compare the value of each tumor marker alone and different combinations in the diagnosis of epithelial ovarian cancer. The clinical data of patients with epithelial ovarian cancer (n=65) and ovarian benign disease (n=29) were collected. Multiple tumor marker protein chip was used to detect cancer antigen 125 (CA125), carbohydrate antigen 242 (CA242), alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-HCG), carcinoembryonic antigen (CEA), cancer antigen 199 (CA199), neuron-specific enolase (NSE), Ferritin, cancer antigen 153 (CA153), and human growth hormone (HGH) serum levels, and to compare the differences between the benign and malignant ovarian tumors. The correlation between tumor markers and clinicopathologic features for ovarian epithelial carcinoma was analyzed by χ2 test. Spearman rank analysis showed the correlation between CA125 expression level and other tumor markers in epithelial ovarian cancer and the correlation between age and the above 10 tumor markers. Sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and diagnostic efficiency were used to evaluate the diagnostic value of single tumor marker and the combination of tumor markers. The levels of β-HCG, NSE, CA153, and CA125 in the epithelial ovarian cancer group were higher than those in the ovarian benign disease group. The level of NSE in the serum of patients with epithelial ovarian cancer was related to the clinical stage of patients. In addition, the levels of CA242, β-HCG, CEA, NSE, Ferritin, CA153 in the serum of patients with epithelial ovarian cancer were positively correlated with CA125 (rs=0.497, P<0.001; rs=0.612, P<0.001; rs=0.358, P=0.003; rs=0.680, P<0.001; rs=0.322, P=0.009; rs=0.609, P<0.001, respectively), and the levels of β-HCG, Ferritin, CA153 were positively correlated with the patient's age (rs=0.256, P=0.040; rs=0.325, P=0.008; rs=0.249, P=0.046, respectively). In the diagnosis of epithelial ovarian cancer, the sensitivity, Youden index, and diagnostic efficiency of CA125 detection alone were higher than the results of the other 9 separate detections. When CA153, CA199, CA242, Ferritin, and CEA were combined with CA125, the sensitivity of the combined detection of different combinations was higher than that of CA125 alone. The combined detection sensitivities of CA125+CEA and CA125+Ferritin+CEA were 89.2% and 90.8%, respectively, and the diagnostic efficiencies were both 84.1%, which were higher than those of other combinations. The Youden index of CA125+CEA joint detection was 0.616, which was higher than those of other combinations. CA125 has a high diagnostic value in the diagnosis of epithelial ovarian cancer. The detection of combined tumor markers in serum has higher sensitivity and specificity in epithelial ovarian cancer.

The performance of Carbohydrate Antigen 125-Thomsen-nouveau and anti-Müllerian hormone combined with CA125, Human epididymis protein 4 and Risk of Malignancy Algorithm in diagnosis for patients with Epithelial ovarian cancer

ObjectivesWe examined the blood concentrations of Carbohydrate Antigen 125-Thomsen-nouveau (CA125-Tn) and anti-Müllerian hormone (AMH) in epithelial ovarian cancer (EOC) patients to evaluate their potential diagnostic utility together with CA125, human epididymis protein 4 (HE4) and Risk of Malignancy Algorithm (ROMA). Design & methods50 healthy subjects, 45 EOC patients, 22 patients with borderline ovarian tumors (BOT), 21 patients with benign ovarian tumor (BET) and 45 patients with chocolate cyst of ovary (CCO) were studied. Blood levels of CA125, HE4, CA125-Tn and AMH were measured, and the ROMA value was calculated. We compared the differences in the levels of these biomarkers among groups. Additionally, a total of 10 testing strategies were established for comparison to maximize the diagnostic value. ResultsThe levels of CA125, HE4, CA125-Tn and ROMA value were significantly higher in EOC group compared with either the disease control (DC) group (BOT group, BET group and CCO group) or healthy control (HC) group (p < 0.001). In addition, they had better discriminatory performance with an area under the receiver operator characteristic curve (AUC) 0.93; 0.93; 0.93; 0.85, respectively (p < 0.001) compared with the AUC value of AMH 0.67 (p < 0.001). Among all 10 testing strategies, both single-positive of ROMA and double-positive of any 2 markers showed better Youden index (0.82, 0.79, respectively) and kappa value (κ) (0.82, 0.81, respectively). ConclusionsCA125-Tn and AMH can be treated as useful biomarkers of EOC when combined with CA125, HE4 and ROMA, because when any two biomarkers of them are positive, the value of EOC diagnosis is maximized.