Non-ovarian Cancer Research Articles

Can CA-125/CEA ratio be used for the differential diagnosis between ovarian and non-ovarian cancers? A cross-sectional study

Can CA-125/CEA ratio be used for the differential diagnosis between ovarian and non-ovarian cancers? A cross-sectional study

Improving Specificity for Ovarian Cancer Screening Using a Novel Extracellular Vesicle–Based Blood Test: Performance in a Training and Verification Cohort

The low incidence of ovarian cancer (OC) dictates that any screening strategy needs to be both highly sensitive and highly specific. This study explored the utility of detecting multiple colocalized proteins or glycosylation epitopes on single tumor-associated extracellular vesicles (EVs) from blood. The novel OC Test employs immunoaffinity capture of tumor-associated EVs followed by proximity-ligation qPCR to detect combinations of up to three biomarkers to maximize specificity and measures multiple combinations to maximize sensitivity. A high-grade serous carcinoma (HGSC) case-control training set of EDTA plasma samples from 397 women was used to lock down the test design, the data interpretation algorithm, and the cut-off between cancer and non-cancer. Performance was verified and compared to CA125 in an independent blinded case-control set of serum samples from 390 women (132 controls, 66 HGSC, 83 non-HGSC OC, 109 benign). In the verification study, the OC Test showed a specificity of 97.0% (128/132; 95% CI: 92.4%-99.6%), a HGSC sensitivity of 97.0% (64/66; 95% CI: 87.8%-99.2%), and an AUC of 0.97 (95% CI 0.93-0.99) and also detected 73.5% (61/83; 95% CI: 62.7%-82.6%) of the non-HGSC OC cases. This test exhibited fewer false positives in subjects with benign ovarian tumors, non-ovarian cancers, and inflammatory conditions when compared to CA125. The combined sensitivity and specificity of this new test suggests it may have potential in OC screening.

Symptoms, distress, finances, social support, resource utilization, and unmet care needs of patients with gynecological cancer

PurposeThis study explored the unmet care needs of gynecological cancer patients, including overall and subdomain needs (i.e., physical and daily living needs, psychological and emotional needs, care and support needs, and health-system and information needs), and related factors. MethodsIn this cross-sectional study, gynecological cancer patients treated at a medical center in northern Taiwan were recruited. Data on demographics, symptoms, distress, finances, social support, resource utilization, and care needs were collected. Spearman's correlation and the Mann–Whitney U test were used for analysis. ResultsThis study of 118 cancer patients found that 73% had unmet psychological and emotional needs, followed by 54% with unmet health system and information needs. The most common physical symptoms were insomnia, fatigue, and pain, with 51.7% experiencing moderate or high levels of distress. Overall, the patients received considerable social support, both instrumental and emotional, primarily through medical information booklets (39.0%), cancer information websites (28.8%), and rehabilitative resources (20.3%). Factors associated with unmet care needs included younger age, non-ovarian cancer, symptoms (pain, fatigue, appetite loss, insomnia, dyspnea, nausea, and vomiting), distress, finances, social support, and the use of cancer information websites. ConclusionPsychological and emotional unmet needs is prevalent among patients with gynecological cancer; psychological support is crucial. Younger patients and those with non-ovarian cancer had more unmet care needs. These needs are linked to severe symptoms, distress, financial difficulties, limited social support, and low use of cancer information websites. Enhancing support for this population through targeted interventions is necessary.

Can CA-125/CEA ratio be used for the differential diagnosis between ovarian and non-ovarian cancers? A research letter.

Can CA-125/CEA ratio be used for the differential diagnosis between ovarian and non-ovarian cancers? A research letter.

The Presence of Ovarian Cancer and the Incidence of Subsequent Open-Angle Glaucoma: A Population-Based Cohort Study.

We aim to explore the possible association between ovarian cancer and the subsequent development of open-angle glaucoma (OAG) using the Taiwan Longitudinal Health Insurance Database (LHID) 2000. A retrospective cohort study was executed, and individuals with ovarian cancer were enrolled and age-matched (with a 1:4 ratio) to non-ovarian cancer individuals. A total of 4990 and 19,960 patients were put into the ovarian cancer and control groups. The main outcome was the presence of OAG according to the LHID 2000 codes. The Cox proportional hazard regression was adopted to demonstrate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) of OAG between the ovarian cancer and control groups. There were a total of 241 and 1029 OAG cases observed in the ovarian cancer group and the control group, respectively. The incidence of OAG was significantly higher in the ovarian cancer group than in the control group according to multivariable analysis (aHR: 1.18, 95% CI: 1.02-1.37, p = 0.022). The ovarian cancer patients older than 60 years showed a significantly higher risk of OAG compared to the non-ovarian cancer individuals of the same age (aHR: 1.39, 95% CI: 1.16-1.63, p = 0.001). Additionally, ovarian cancer individuals with a disease interval of more than two years presented a significantly higher incidence of OAG than the non-ovarian cancer group (p < 0.05). In conclusion, ovarian cancer positively correlates with a high rate of subsequent OAG, especially in elderly persons with a long disease interval.

The Associations and Causal Relationships of Ovarian Cancer - Construction of a Prediction Model.

To explore the risk and protective factors for developing ovarian cancer and construct a risk prediction model. Information related to patients diagnosed with ovarian cancer on the electronic medical record data platform of three tertiary hospitals in Guangdong Province from May 2018 to September 2023 was collected as the case group. Patients with non-ovarian cancer who attended the clinic during the same period were included in the control group. Logistic regression analysis was used to screen the independent variables and explore the factors associated with the development of ovarian cancer. An ovarian cancer risk prediction model was constructed using a decision tree C4.5 algorithm. The ROC and calibration curves were plotted, and the model was validated. Logistic regression analysis identified independent risk and protective factors for ovarian cancer. The sample size was divided into training and test sets in a ratio of 7:3 for model construction and validation. The AUC of the training and test sets of the decision tree model were 0.961 (95% CI:0.944-0.978) and 0.902 (95% CI:0.840-0.964), respectively, and the optimal cut-off values and their coordinates were 0.532 (0.091, 0.957), and 0.474 (0.159, 0.842) respectively. The accuracies of the training and test sets were 93.3% and 84.2%, respectively, and their sensitivities were 95.7% and 84.2%, respectively. The constructed ovarian cancer risk prediction model has good predictive ability, which is conducive to improving the efficiency of early warning of ovarian cancer in high-risk groups.

The Association between Ovarian Cancer and the Incidence of Newly Developed Dry Eye Disease: A Nationwide Population-Based Study.

We aim to investigate the potential correlation between the presence of ovarian cancer and the development of dry eye disease (DED) via the usage of the Longitudinal Health Insurance Database (LHID) of Taiwan. A retrospective cohort study was executed, and patients with ovarian cancer were selected according to the diagnostic and procedure codes. One ovarian cancer patient was matched to four non-ovarian cancer participants which served as control group, and a total of 4992 and 19,968 patients constructed the ovarian cancer and control groups, respectively. The primary outcome in the current study is the development of DED according to the diagnostic and procedure codes. Cox proportional hazard regression was utilized to produce the adjusted hazard ratio (aHR) and related 95% confidence interval (CI) of DED between the two groups. There were 542 and 2502 DED events observed in the ovarian cancer group and the control group, respectively. The ovarian cancer group illustrated a significantly higher incidence of DED development than the control group after the adjustment of several confounders (aHR: 1.10, 95% CI: 1.01-1.21, p = 0.040). In the subgroup analysis stratified by age, ovarian cancer patients aged older than 60 years showed a higher incidence of DED compared to the non-ovarian cancer population (aHR: 1.19, 95% CI: 1.08-1.28, p = 0.011). In addition, ovarian cancer patients with a disease duration longer than five years also showed higher incidence of DED formation than the non-ovarian cancer population (aHR: 1.13, 95% CI: 1.04-1.22, p = 0.027). In conclusion, the presence of ovarian cancer is associated with higher incidence of subsequent DED, especially in those older than 60 years and with a disease interval of more than five years.

Abstract 6406: Clinical and translational results of the academic ARIANES Phase 2 basket study: Longitudinal single-cell analysis of patient tumors identifies biological correlates of response to PARP inhibitors and anti-PD-L1 therapy

Abstract Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) have immunomodulatory properties that may potentiate anti-PD-L1 therapy. To explore this, we developed the academic ARIANES phase 2 basket trial, which evaluated the PARPi rucaparib (R) and the anti-PD-L1 atezolizumab (A) in selected patients (pts). We performed single-cell RNA + T cell receptor sequencing (scRNA+TCR-seq) on 3 sequential tumor biopsies in a pts subset. Methods: ARIANES comprised 4 molecularly-selected DNA damage response deficient (DDRd), 3 platinum-sensitive, and 2 unselected cohorts of pts with non-small cell lung (NSCLC), prostate (CRPC), and other non-breast non-ovarian cancers. R was administered for 3 weeks, followed by R+A. Primary endpoint was overall response rate (ORR) at 12 weeks per cohort. scRNA+TCR-seq was performed on fresh biopsies collected at baseline, on R, and on R + A in the same lesion, with concomitant plasma collection. We tracked the evolution over time of tumor and microenvironment cells, differentially expressed genes and signatures within each cell population, and TCR clonal dynamics. Results: ARIANES enrolled 130 pts, including 27 DDRd CRPC and 3 DDRd NSCLC pts, on which we focus here. Best ORR by RECIST v1.1 was 22% (6/27) in CRPC pts, and mPFS: 7.9 months (95% CI 4 - 11.1) at data cut-off. ORR was 0% in NSCLC pts. We successfully profiled 3 sequential fresh biopsies in 2 BRCA2-mutant CRPC, 1 ATM-mutant, and 1 RAD54L-mutant NSCLC pts. Tumor, T and B lymphoid, myeloid, plasma, dendritic, NK, endothelial, and stromal cells were identified in all samples. Differential expression testing unveiled PARP1 upregulation in tumor cells on R. One CRPC pt with prolonged partial response displayed activation of innate immune sensing pathways (including cGAS-STING and IFN signaling) in tumor and immune cells, as well as JAK/STAT and CCL5, all increasing gradually on R and R + A; scTCR-seq revealed the expansion of specific T cell clonotypes on R + A. One ATM-mutant NSCLC pt with 6-month stable disease displayed increased cGAS/STING, JAK/STAT and CCL5 activation on R in NK cells only, and no TCR expansion. None of the above was observed in the 2 pts who progressed. Complete clinical and translational study results will be presented at the congress. Conclusion: Sequential scRNA+TCR-seq enables the dynamic assessment of tumor and immune cells on therapy. Our data confirms the potential of R to activate innate immune pathways in pt tumors, and R + A to induce T cell activation and clonal expansion. To our knowledge, this is the first study providing a longitudinal single-cell resolution analysis of the clonal evolution of tumor and immune cells in pts on PARPi + anti-PD-L1. We identify potential biological correlates of therapy response, including the activation of innate immune pathways and TCR expansion. Citation Format: Julien Vibert, Clémence Hénon, Lambros Tselikas, Baptiste Bonnet, Arnaud Pagès, Alice Bernard-Tessier, Léo Colmet-Daage, Roman Chabanon, Nicolas Dorvault, Clémence Astier, Anas Gazzah, Aurore Jeanson, Aurélien Parpaleix, Ronan Flippot, Natacha Naoun, Anna Patrikidou, Pernelle Lavaud, Giulia Baciarello, Emeline Colomba, Alina Fuerea, Laurence Albiges, Christophe Massard, Santiago Ponce, Yohann Loriot, Stéphane Champiat, Capucine Baldini, Fanny Bouquet, Nathalie Droin, Karim Fizazi, Damien Vasseur, Patricia Martin-Romano, Etienne Rouleau, Kaïssa Ouali, Sophie Postel-Vinay. Clinical and translational results of the academic ARIANES Phase 2 basket study: Longitudinal single-cell analysis of patient tumors identifies biological correlates of response to PARP inhibitors and anti-PD-L1 therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6406.

PARP inhibitors in non-ovarian gynecologic cancers.

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPis) have transformed the treatment of ovarian cancer, particularly benefiting patients whose tumors harbor genomic events that result in impaired homologous recombination (HR) repair. The use of PARPi over recent years has expanded to include subpopulations of patients with breast, pancreatic, and prostate cancers. Their potential to benefit patients with non-ovarian gynecologic cancers is being recognized. This review examines the underlying biological rationale for exploring PARPi in non-ovarian gynecologic cancers. We consider the clinical data and place this in the context of the current treatment landscape. We review the development of PARPi strategies for treating patients with endometrial, cervical, uterine leiomyosarcoma, and vulvar cancers. Furthermore, we discuss future directions and the importance of understanding HR deficiency in the context of each cancer type.

Risks of non-ovarian cancers in women with borderline ovarian tumor: a national cohort study in Sweden

BackgroundAssociations between different cancer types are known. The affirmation of the risk for non-ovarian cancer after ovarian borderline tumors (BOT) is, however, sparse.AimTo analyze the risk of subsequent or simultaneous cancers in women with BOTs compared with the general female Swedish population.MethodsAn open cohort study (1995–2018) was conducted where a diagnosis of BOTs as well as subsequent or simultaneous cancer diagnoses were obtained from the Swedish Cancer Register and matched to the Total Population Register. Each woman with BOT was followed until non-ovarian cancer, death or emigration and could only be included once for the outcome. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for specific non-ovarian cancers were analyzed.ResultsThe 4998 women with serous and mucinous BOTs were diagnosed during 1995–2018 with a mean age of 55.7 years (SD 16.0) at diagnosis. Compared with the general female population, women with BOTs had increased risks for non-ovarian cancer in colon (SIR = 2.5; 95% CI 2.0–3.1), rectum (SIR = 1.7; 95% CI 1.1–2.5), small intestine (SIR = 5.0; 95% CI 2.3–9.5), cervix (SIR = 2.5; 95% CI 1.4–4.2), endometrium (SIR = 2.4; 95% CI 1.9–3.1), pancreas (SIR = 2.3; 95% CI 1.4–3.5), upper aerodigestive tract (SIR = 2.2; 95% CI 1.2–3.8), lung (SIR = 1.8; 95% CI 1.4–2.3), kidney (SIR = 2.3; 95% CI 1.4–3.7) and bladder (SIR = 1.8; 95% CI 1.1–2.8). Among women with serous BOTs, the risk of thyroid gland cancer (SIR = 3.1; 95% CI 1.2–6.4) was also increased. Lung and pancreas cancer showed increased risks more than 1 year after a diagnosis of BOT.ConclusionsThis Swedish population-based study demonstrated an increased risk of multiple malignancies including lung and pancreatic cancers beyond the first year of diagnosis in patients with borderline ovarian tumors (BOTs), suggesting a potential shared etiology.

Talazoparib (Tala) in patients (pts) with solid tumors with BRCA1/2 mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study.

3115 Background: TAPUR is a phase II basket study evaluating antitumor activity of commercially available targeted agents in pts with advanced cancers with specific genomic alterations. Results in a cohort of pts with solid tumors with BRCA1/2 mut treated with Tala are reported. Methods: Eligible pts had measurable disease, ECOG performance status (PS) 0-2, adequate organ function, and no standard treatment (tx) options. Genomic testing was performed in CLIA-certified, CAP-accredited site selected labs. Pts received 1 mg of Tala orally daily until disease progression. Primary endpoint was disease control (DC) per investigator defined as complete (CR) or partial (PR) response or stable disease (SD) of at least 16+ weeks (wks) duration (SD16+) per RECIST v1.1. The hypothesized null DC rate of 15% was evaluated by a 1-sided exact binomial test (alpha 0.10; 82% power). Secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DOR) and SD, and safety. DOR is defined as time from pt’s first documented objective response (OR) to progressive disease (PD). Duration of SD is defined as time from tx start to PD. Results: 28 pts with 16 solid tumors (6/28 pts had lung cancer) with BRCA1 (n=9) , BRCA2 (n=16) , or BRCA1/2 (n=3) mut were enrolled from Dec 2019 to Sept 2021. All pts were included in efficacy analyses. Demographics and outcomes are shown. 1 CR, 9 PR and 6 SD16+ were observed for a DC rate of 57% (1-sided 90% CI: 43% to 100%) and an OR rate of 36% (95% CI: 19% to 56%); the null hypothesis of a 15% DC rate was rejected (p&lt;0.001). 11/16 pts with OR or SD16+ had a BRCA2 mut, 4 had BRCA1 mut, and 1 had both. The pt with a CR (duration of 93 wks) had non-melanoma skin cancer, with BRCA2 and ATM muts, and was microsatellite instability high with 41 muts per megabase. Pts with PR had various solid tumors; 6/9 pts had BRCA2 mut, 2 had BRCA1 mut , 1 had both. Of pts with DC, 11 had tumor types for which PARP inhibitors are not yet FDA approved. Median duration of PR was 20 wks (range, 11-80). 10/16 pts with DC had a co-alteration in the 24 homologous recombination-related genes examined, mainly ATM (3) or ARID1A (2). 13 pts had ≥1 grade 3 tx-related adverse or serious adverse events including: anemia, AST or bilirubin increase, hyponatremia, nausea, vomiting, neutrophil, platelet, or white blood cell decrease. Conclusions: Tala demonstrated antitumor activity in heavily pretreated pts with advanced solid tumors with BRCA1/2 mut. Additional study is warranted to confirm the efficacy of Tala in non-breast, non-ovarian cancer pts with BRCA1/2 mut. Clinical trial information: NCT02693535 . [Table: see text]

Current Methods and Advances in the Immunotherapy Treatment of Non-Ovarian Gynaecological Cancers

Endometrial cancer (EC) and cervical cancer (CC) are common malignancies in women in clinical practice. More uncommon non-ovarian malignancies, such as vulval cancer (VC), are also becoming more prevalent in women of all ages. Currently, there are few comprehensive reviews on the management of these conditions, despite the recent advances in the use of immunotherapy in the management of other forms of cancer. The treatment modalities for EC, CC and VC vary; however, platinum-based chemotherapy, surgical resection and radiotherapy are the main forms of treatment. In more advanced or recurrent disease, there is a limited number of efficacious treatments, with many clinicians relying on adjuvant chemotherapy despite the increased rationale for the use of immunotherapy. With the development of the novel adoptive T-cell therapy, intra-tumoural oncolytic viral therapy and cancer vaccines, the landscape of gynaecological cancer management is changing, and it is likely that treatment efficacy and outcomes will improve dramatically. This review aims to summarise the current management of endometrial, cervical and vulval cancer and to evaluate the novel therapies under development, as well as the future of the management of non-ovarian gynaecological malignancies.

Claudin18.2 as a potential therapeutic target for primary ovarian mucinous carcinomas and metastatic ovarian mucinous carcinomas from upper gastrointestinal primary tumours

BackgroundThe vast majority of ovarian mucinous carcinomas are metastatic tumours derived from nonovarian primary cancers, typically gastrointestinal neoplasms. Therapy targeting claudin18.2 might be used in gastric, gastroesophageal junction and pancreatic cancers with high expression of claudin18.2. In this study, we aimed to profile the expression of claudin18.2 in primary ovarian mucinous carcinoma (POMC) and metastatic gastrointestinal mucinous carcinoma (MGMC).MethodsImmunohistochemistry was used to detect claudin 18.2 expression in whole tissue sections of ovarian mucinous carcinomas, including 32 POMCs and 44 MGMCs, 23 of which were derived from upper gastrointestinal primary tumours and 21 of which were derived from lower gastrointestinal primary tumours. Immunohistochemical studies for claudin18.2, SATB2, PAX8, CK7 and CK20 were performed in all 76 cases.ResultsAmong 76 primary and metastatic mucinous carcinomas, claudin18.2 was expressed in 56.6% (43/76) of cases. MGMCs from the upper gastrointestinal tract, including 22 derived from primary stomach tumours and one derived from a pancreas tumour, were positive for claudin 18.2 in 69.5% (16/23) of cases. MGMCs from the lower gastrointestinal tract, including 10 derived from primary appendiceal cancer and 11 derived from colorectal cancers, showed no claudin18.2 expression (0/21). The expression rate of claudin18.2 in primary ovarian mucinous neoplasms, including 22 primary ovarian mucinous carcinomas and 10 primary ovarian borderline mucinous tumours, was 84.4% (27/32). The common immunophenotypic characteristics of POMCs, upper gastrointestinal tract-derived MGMCs, and lower gastrointestinal tract-derived MGMCs were claudin18.2 + /PAX8 + /SATB2- (17/32), claudin18.2 + /PAX8-/SATB2- (16/23) and claudin18.2-/PAX8-/SATB2 + (19/21), respectively.ConclusionClaudin18.2 is highly expressed in POMCs and MGMCs derived from upper gastrointestinal tract primary tumours; therefore, claudin18.2-targeted therapy might serve as a potential therapeutic strategy for POMCs and MGMCs from the upper gastrointestinal tract.

Risk of nonovarian cancer in a nationwide-based study of nearly 5000 women with borderline ovarian tumors in Denmark.

Evidence regarding cancer risk after borderline ovarian tumors (BOTs) is limited. We conducted a nationwide cohort study examining the incidence of nonovarian cancers in women with serous or mucinous BOTs compared with the general female population with up to 41 years of follow-up. Through the nationwide Pathology Registry, we identified nearly 5000 women with BOTs (2506 serous and 2493 mucinous) in Denmark, 1978 to 2018. We computed standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) as relative risk estimates of specific nonovarian cancers. Compared with general female population rates, women with serous BOTs had increased rates of particularly malignant melanoma (SIR=1.9; 95% CI: 1.3-2.6), thyroid cancer (SIR=3.0; 95% CI: 1.4-5.4) and myeloid leukemia (SIR=3.2; 95% CI: 1.5-5.8), and women with mucinous BOTs had elevated rates of lung cancer (SIR=1.7; 95% CI: 1.3-2.1), pancreatic cancer (SIR=1.9; 95% CI: 1.2-2.9) and myeloid leukemia (SIR=2.3; 95% CI: 0.9-4.7). We found no convincing association with neither breast nor colorectal cancer in women with BOTs. This is the first large nationwide study showing that women with specific types of BOTs have increased risks of several nonovarian cancers, likely due to some shared risk factors or genetic characteristics.

Identification and Validation of the Diagnostic Characteristic Genes of Ovarian Cancer by Bioinformatics and Machine Learning.

Background: Ovarian cancer (OC) has a high mortality rate and poses a severe threat to women’s health. However, abnormal gene expression underlying the tumorigenesis of OC has not been fully understood. This study aims to identify diagnostic characteristic genes involved in OC by bioinformatics and machine learning. Methods: We utilized five datasets retrieved from the Gene Expression Omnibus (GEO) database, The Cancer Genome Atlas (TCGA) database, and the Genotype-Tissue Expression (GTEx) Project database. GSE12470 and GSE18520 were combined as the training set, and GSE27651 was used as the validation set A. Also, we combined the TCGA database and GTEx database as validation set B. First, in the training set, differentially expressed genes (DEGs) between OC and non-ovarian cancer tissues (nOC) were identified. Next, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were performed for functional enrichment analysis of these DEGs. Then, two machine learning algorithms, Least Absolute Shrinkage and Selector Operation (LASSO) and Support Vector Machine-Recursive Feature Elimination (SVM-RFE), were used to get the diagnostic genes. Subsequently, the obtained diagnostic-related DEGs were validated in the validation sets. Then, we used the computational approach (CIBERSORT) to analyze the association between immune cell infiltration and DEGs. Finally, we analyzed the prognostic role of several genes on the KM-plotter website and used the human protein atlas (HPA) online database to analyze the expression of these genes at the protein level. Results: 590 DEGs were identified, including 276 upregulated and 314 downregulated DEGs.The Enrichment analysis results indicated the DEGs were mainly involved in the nuclear division, cell cycle, and IL−17 signaling pathway. Besides, DEGs were also closely related to immune cell infiltration. Finally, we found that BUB1, FOLR1, and PSAT1 have prognostic roles and the protein-level expression of these six genes SFPR1, PSAT1, PDE8B, INAVA and TMEM139 in OC tissue and nOC tissue was consistent with our analysis. Conclusions: We screened nine diagnostic characteristic genes of OC, including SFRP1, PSAT1, BUB1B, FOLR1, ABCB1, PDE8B, INAVA, BUB1, TMEM139. Combining these genes may be useful for OC diagnosis and evaluating immune cell infiltration.

Factors associated with serum CA125 level in women without ovarian cancer in the United States: a population-based study

BackgroundCancer antigen 125 (CA125) is clinically used to monitor response to therapy in ovarian cancer and has been proposed for use in detecting ovarian cancer. This population-based study examines how demographic characteristics, gynecologic/reproductive history, chronic non-malignant medical conditions, history of non-ovarian cancer, lifestyle practices, and biomarkers of inflammation correlate with serum CA125 in both premenopausal and postmenopausal women without ovarian cancer across the United States.MethodsParticipants were identified from the National Health and Nutrition Examination Survey 2001–2002. Linear and logistic regression models were applied.ResultsHigher CA125 levels were found to correlate with younger age, Non-Hispanic White race/ethnicity, and lower body mass index. In premenopausal women (N = 1157), current smoking was associated with lower CA125 (− 24.95%, p = 0.008), and history of non-ovarian cancer was associated with higher CA125 (40.64%, p = 0.045) by multivariable linear regression; both current smoking (odds ratio (OR) = 0.42, p = 0.043) and oral contraceptive pill (OCP) use of 5–10 years (OR = 0.31, p = 0.032) were less likely to be associated with having CA125 level ≥ 35 U/ml by multivariable logistic regression. In postmenopausal women (N = 1116), coronary artery disease (CAD) history was associated with higher CA125 (28.27%, p = 0.047) by multivariable linear regression; history of CAD (OR = 5.00, p = 0.011), history of breastfeeding (OR = 2.46, p = 0.026), and increased CRP level (OR = 1.41, p = 0.042) were more likely to be associated with having CA125 level ≥ 35 U/ml by multivariable logistic regression.ConclusionsResults suggest CA125 is lower in premenopausal women who are current smokers and OCP users of moderately longer duration but higher in those with non-ovarian cancer. CA125 is higher in those postmenopausal women with CAD, history of breastfeeding and elevated CRP level. These associations can inform clinical interpretation of individual patients’ CA125 levels.

Algorithm to Identify Incident Epithelial Ovarian Cancer Cases Using Claims Data.

To create an algorithm to identify incident epithelial ovarian cancer cases in claims-based data sets and evaluate performance of the algorithm using SEER-Medicare claims data. We created a five-step algorithm on the basis of clinical expertise to identify incident epithelial ovarian cancer cases using claims data for (1) ovarian cancer diagnosis, (2) receipt of platinum-based chemotherapy, (3) no claim for platinum-based chemotherapy but claim for tumor debulking surgery, (4) removed cases with nonplatinum chemotherapy, and (5) removed patients with prior claims with personal history of ovarian cancer code to exclude prevalent cases. We evaluated algorithm performance using SEER-Medicare claims data by creating four cohorts: incident epithelial ovarian cancer, a 5% random sample of cancer-free Medicare beneficiaries, a 5% random sample of incident nonovarian cancer, and prevalent ovarian cancer cases. Using SEER tumor registry data as the gold standard, our algorithm correctly classified 89.9% of incident epithelial ovarian cancer cases (cohort n = 572) and almost 100% of cancer-free controls (n = 97,127), nonovarian cancer (n = 714), and prevalent ovarian cancer cases (n = 3,712). The overall algorithm sensitivity was 89.9%, the positive predictive value was 93.8%, and the specificity and negative predictive value were > 99.9%. Patients were more likely to be correctly classified as incident ovarian cancer if they had stage III or IV disease compared with early stage I or II disease (93.5% v 83.7%, P < .01), and grade 1-4 compared with unknown grade tumors (93.8% v 81.4%, P < .01). Our algorithm correctly identified most incident epithelial ovarian cancer cases, especially those with advanced disease. This algorithm will facilitate research in other claims-based data sets where cancer registry data are unavailable.

Predictors of malignancy in incidental adnexal lesions identified on CT in patients with prior non-ovarian cancer.

To identify imaging features in incidental adnexal lesions which are associated with malignancy on portal venous phase contrast-enhanced CT in patients with known non-ovarian cancer. This IRB-approved, HIPAA-compliant retrospective study was performed at a tertiary cancer center. Portal venous phase contrast-enhanced CT from January 2010 to December 2015 was reviewed to identify women with non-ovarian malignancy and incidental adnexal lesion, with mean 18months (range 1-80months) to definitive diagnosis or last imaging follow-up. Imaging features of adnexal lesions were recorded (size, laterality, shape, attenuation, and composition) and correlated with outcome (benign or malignant) using univariate and multivariate logistic regression analysis. A point-based system was used to predict likelihood of malignancy. Of 276 women (mean age 45years), 216 (78.3%) had benign lesions, 58 (21.0%) ovarian metastasis, and 2 (0.7%) had primary ovarian malignancy. On logistic regression model, lesion size > 5cm (p-value, OR, 95% CI 0.01, 9.11, 1.70-48.87), bilaterality (< 0.0001, 28.34, 7.46-107.67), irregular shape (0.01, 12.31, 1.61-94.05), higher-than-simple-fluid attenuation (< 0.0001, 28.27, 5.65-141.59), and heterogeneous composition (0.0017, 10.75, 2.45-47.23) were associated with malignant outcome (AUC 0.97). A point-based system incorporating these five features (possible 0-5 points) had AUC of 0.97. Rate of malignancy was 0% (0/147) if none of the features of malignancy were present, 12.7% (8/63) if one feature was present, 51.7% (15/29) if two features were present, and 100% (37/37) if three or more features present. Risk of malignancy of incidental adnexal lesions in women with prior non-ovarian cancer can be estimated based on lesion features seen on portal venous phase contrast-enhanced CT.

YOUNG WOMEN DIAGNOSED WITH DISTAL CANCER SHOW TELOMERE ALTERATIONS IN THE OVARY

Telomeres play an essential role in the protection of chromosomes. Telomere length (TL) decreases progressively with age, limiting the number of cell divisions and inducing cellular senescence or apoptosis. The loss of telomere protection (TP), which depends on the Shelterin complex, leads to a state of genomic instability that can promote cancer. The aim of this study is to determine whether the telomere pathway is altered in the ovary of women with distal cancer at the time of diagnosis, and the possible role of peripheral blood mononuclear cells (PBMC) TL as biomarker of fertility. 15 women with non-ovarian cancer (Cn) and 13 controls (Ct) were recruited at the Hospital La Fe (Valencia). Ovarian biopsies and blood samples were obtained before therapy. Ovarian biopsies were collected during process of fertility preservation in patients, and in controls, during tubal ligation. Ovarian samples were embedded in paraffin. Blood cells were processed with a Ficoll gradient to isolate PBMC. Telomere length was measured by Fluorescence in Situ Hybridization (FISH), and TP was analyzed by immunofluorescence of the TRF1 Shelterin. Participants were divided into two groups, young women (<33 years old, Y) and older women (>33 years old, O). Mean age and anti-mullerian hormone (AMH) of controls and patients were: YCt (30 ± 3.55 years, 3.87 ± 2.09 ng/mL) and OCt (37.6 ± 2.11 years, 3.87 ± 2.44 ng/mL); YCn (25.18 ± 6.24 years, 3.72 ± 1.92 ng/mL) and OCn (36 ± 1.82 years, 1.29 ± 0.55 ng/mL). Regarding younger women, ovarian TL was higher in controls than in patients (42.62 ± 3.91 and 39.61 ± 3.25 a.u., respectively). In PBMC, similar results were obtained (controls 86.54 ± 9.29 and patients 75.21 ± 14.26 a.u.), but TL differences were not statistically significant. Both ovarian and blood TL showed a positive correlation trend. Ovarian TP was higher in controls than in patients (47.14 ± 4.14 and 43.34 ± 4.32 a.u., respectively), but this trend was not observed in PBMC. Regarding older women, no differences were observed between controls and patients in TL or TP in the ovary. However, in PBMC from the control group TL was higher than in patients (79.75 ± 9.86 and 76.87 ± 4.44 a.u., respectively). In addition, a better TP was found in controls compared to patients (354.5 ± 154 and 274.6 ± 25.49 a.u., p = 0.0132). TL shows a tendency to be shorter in non-ovarian cancer patients than in controls, this difference is observed at the ovarian and blood levels in young women. TP tends to be lower in the ovary of young women with cancer than in controls of the same age group. This suggests a systemic effect of cancer both at the ovary and blood levels in young women. In older women, differences in TL between controls and patients were harder to find. Possibly a higher number of older patients would clarify the results.

Little Clinical Relevance of Ca125, Cea and Ca125/Cea Ratio for the Differential Diagnosis of Ovarian and Non- Ovarian Carcinomatosis

Background In women, peritoneal cancer is commonly associated to epithelial ovarian cancer. Ovarian peritoneal carcinomatosis patient survival appears to be better in comparison to other peritoneal Malignancies, e.g., colorectal neoplasms or mesotheliomas. Here, we aim to analyze the value of CA125, CEA, CA125/CEA ratio (CCR) tumor markers as preoperative tools for the diagnosis ovarian cancer. Material and methods: From 2005-2008, we recruit prospectively patients admitted to the Navarre Hospital Complex Gynecological service with peritoneal carcinomatosis and suspicion of ovarian cancer origins. The final diagnosis of ovarian cancer carcinomatosis or other malignancies was obtained through Biopsy or cytology. CA 125, CEA and CCR were determined from preoperative venous blood Samples. We compared the tumor markers values between groups of ovarian cancer carcinomatosis and non-ovarian cancer carcinomatosis and calculate the receiver operating curves (ROC) for CA 125, CEA and CCR. Results From 250 patients with suspicion of having ovarian peritoneal carcinomatosis, only 86.4% of the Cases were finally diagnosis of ovarian cancer. Sensitivities of CA125 &gt; 35 mg/dL, CEA &lt; 5 ngr/mL, and CCR &gt; 25 were 95.5%, 91.9%, and 93.6% with specificities of 4.6%, 40.9% and 40.0%, respectively. ROC displayed poor performance for CA125 and CEA for detecting ovarian peritoneal carcinomatosis patients (area under the curve (AUC): 0.69 and 0.63, respectively) while ROC analysis of CCR showed better results (AUC: 0.74). Conclusions: CCR is somehow useful to differentiate between ovarian and non-ovarian peritoneal carcinomatosis patients in comparison with CA125 and CEA alone, although without sufficient specificity for improving the differential diagnosis.