Autoanitbody Biomarkers for the Early Detection of Serous Ovarian Cancer
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PROVIDER: PRJNA316072 | ENA |
REPOSITORIES: ENA
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Project description:Introduction: Serous ovarian cancer is the leading cause of gynecological cancers, with a 5-year survival rate below 45% due in part to the nonspecific symptoms and lack of accurate screening for early detection. In comparison, patients diagnosed at an early stage have a five-year survival rate of 92%, demonstrating the urgent need for biomarkers for the early detection of disease. Serum from patients with serous ovarian cancer contain antibodies to tumor antigens that are potential biomarkers for early detection. The purpose of this study is to identify a panel of novel serum autoantibody (AAb) biomarkers for the early diagnosis of serous ovarian cancer. Methods: To detect AAb we probed high-density programmable protein microarrays (NAPPA) containing 10,247 antigens with sera from patients with serous ovarian cancer (n = 30 cases/ 30 healthy controls) and measured bound IgG. We identified 735 promising tumor antigens using cutoff values of 10% sensitivity at 95% specificity and K-value>0.8, as well as visual analysis and evaluated these with an independent set of serous ovarian cancer sera (n = 30 cases/ 30 benign disease controls/ 30 heathy controls). Thirty-nine potential tumor autoantigens were identified with sensitivities ranging from 3 to 39.7% sensitivity at 95% specificity and were retested using an orthogonal programmable ELISA assay. A total of 13 potential tumor antigens were identified for further validation using an independent ovarian cancer sera set (n = 44 cases/ 34 healthy controls). Sensitivities at 95% specificity were calculated and a serous ovarian cancer classifier was constructed. In addition, we evaluated a longitudinal study using blinded serous pre-diagnostic ovarian cancer sera (n = 9 cases/ 90 controls) to examine the value of three (CTAG1, CTAG2, and p53) of these AAb in comparison to CA 125. Results: We identified 11-AAbs (ICAM3, CTAG2, p53, STYXL1, PVR, POMC, NUDT11, TRIM39, UHMK1, KSR1, and NXF3) that distinguished serous ovarian cancer cases from healthy controls with a combined 45% sensitivity at 100% specificity. In our longitudinal analysis, p53- and CTAG-AAb were detected up to 9 months prior to ovarian cancer diagnosis and increased with CA 125 levels. Conclusion: These are potential circulating biomarkers for the early detection of serous ovarian cancer, and warrant confirmation in larger clinical cohorts. In addition, p53- and CTAG1/2-AAb are detected in a subset of women with ovarian cancer up to 9 months prior to clinical diagnosis. Their utility as a biomarker for early detection, beyond CA 125, warrant further investigation.
2017-06-01 | GSE79517 | GEO
Project description:Introduction: Serous ovarian cancer is the leading cause of gynecological cancers, with a 5-year survival rate below 45% due in part to the nonspecific symptoms and lack of accurate screening for early detection. In comparison, patients diagnosed at an early stage have a five-year survival rate of 92%, demonstrating the urgent need for biomarkers for the early detection of disease. Serum from patients with serous ovarian cancer contain antibodies to tumor antigens that are potential biomarkers for early detection. The purpose of this study is to identify a panel of novel serum autoantibody (AAb) biomarkers for the early diagnosis of serous ovarian cancer. Methods: To detect AAb we probed high-density programmable protein microarrays (NAPPA) containing 10,247 antigens with sera from patients with serous ovarian cancer (n = 30 cases/ 30 healthy controls) and measured bound IgG. We identified 735 promising tumor antigens using cutoff values of 10% sensitivity at 95% specificity and K-value>0.8, as well as visual analysis and evaluated these with an independent set of serous ovarian cancer sera (n = 30 cases/ 30 benign disease controls/ 30 heathy controls). Thirty-nine potential tumor autoantigens were identified with sensitivities ranging from 3 to 39.7% sensitivity at 95% specificity and were retested using an orthogonal programmable ELISA assay. A total of 13 potential tumor antigens were identified for further validation using an independent ovarian cancer sera set (n = 44 cases/ 34 healthy controls). Sensitivities at 95% specificity were calculated and a serous ovarian cancer classifier was constructed. In addition, we evaluated a longitudinal study using blinded serous pre-diagnostic ovarian cancer sera (n = 9 cases/ 90 controls) to examine the value of three (CTAG1, CTAG2, and p53) of these AAb in comparison to CA 125. Results: We identified 11-AAbs (ICAM3, CTAG2, p53, STYXL1, PVR, POMC, NUDT11, TRIM39, UHMK1, KSR1, and NXF3) that distinguished serous ovarian cancer cases from healthy controls with a combined 45% sensitivity at 100% specificity. In our longitudinal analysis, p53- and CTAG-AAb were detected up to 9 months prior to ovarian cancer diagnosis and increased with CA 125 levels. Conclusion: These are potential circulating biomarkers for the early detection of serous ovarian cancer, and warrant confirmation in larger clinical cohorts. In addition, p53- and CTAG1/2-AAb are detected in a subset of women with ovarian cancer up to 9 months prior to clinical diagnosis. Their utility as a biomarker for early detection, beyond CA 125, warrant further investigation.
2017-06-01 | GSE79516 | GEO
Project description:Introduction: Serous ovarian cancer is the leading cause of gynecological cancers, with a 5-year survival rate below 45% due in part to the nonspecific symptoms and lack of accurate screening for early detection. In comparison, patients diagnosed at an early stage have a five-year survival rate of 92%, demonstrating the urgent need for biomarkers for the early detection of disease. Serum from patients with serous ovarian cancer contain antibodies to tumor antigens that are potential biomarkers for early detection. The purpose of this study is to identify a panel of novel serum autoantibody (AAb) biomarkers for the early diagnosis of serous ovarian cancer. Methods: To detect AAb we probed high-density programmable protein microarrays (NAPPA) containing 10,247 antigens with sera from patients with serous ovarian cancer (n = 30 cases/ 30 healthy controls) and measured bound IgG. We identified 735 promising tumor antigens using cutoff values of 10% sensitivity at 95% specificity and K-value>0.8, as well as visual analysis and evaluated these with an independent set of serous ovarian cancer sera (n = 30 cases/ 30 benign disease controls/ 30 heathy controls). Thirty-nine potential tumor autoantigens were identified with sensitivities ranging from 3 to 39.7% sensitivity at 95% specificity and were retested using an orthogonal programmable ELISA assay. A total of 13 potential tumor antigens were identified for further validation using an independent ovarian cancer sera set (n = 44 cases/ 34 healthy controls). Sensitivities at 95% specificity were calculated and a serous ovarian cancer classifier was constructed. In addition, we evaluated a longitudinal study using blinded serous pre-diagnostic ovarian cancer sera (n = 9 cases/ 90 controls) to examine the value of three (CTAG1, CTAG2, and p53) of these AAb in comparison to CA 125. Results: We identified 11-AAbs (ICAM3, CTAG2, p53, STYXL1, PVR, POMC, NUDT11, TRIM39, UHMK1, KSR1, and NXF3) that distinguished serous ovarian cancer cases from healthy controls with a combined 45% sensitivity at 100% specificity. In our longitudinal analysis, p53- and CTAG-AAb were detected up to 9 months prior to ovarian cancer diagnosis and increased with CA 125 levels. Conclusion: These are potential circulating biomarkers for the early detection of serous ovarian cancer, and warrant confirmation in larger clinical cohorts. In addition, p53- and CTAG1/2-AAb are detected in a subset of women with ovarian cancer up to 9 months prior to clinical diagnosis. Their utility as a biomarker for early detection, beyond CA 125, warrant further investigation.
2017-06-01 | GSE79498 | GEO
Project description:High grade serous ovarian carcinoma (HGSOC) accounts for ~70% of ovarian cancer cases. Non-invasive, highly specific blood-based tests for pre-symptomatic screening in women are crucial to reducing the mortality associated with this disease. Since most HGSOCs typically arise from the fallopian tubes (FT), our biomarker search focused on proteins found on the surface of extracellular vesicles (EVs) released by both FT and HGSOC tissue explants and representative cell lines. Using mass spectrometry, 985 EV proteins (exo-proteins) were identified that comprised the FT/HGSOC EV core proteome. Transmembrane exo-proteins were prioritized because these could serve as antigens for capture and/or detection. With a nano-engineered microfluidic platform, six newly discovered exo-proteins (ACSL4, IGSF8, ITGA2, ITGA5, ITGB3, MYOF) plus a known HGSOC associated protein, FOLR1 exhibited classification performance ranging from 85-98% in a case-control study using plasma samples representative of early (including stage IA/B) and late stage (stage III) HGSOCs. Furthermore, by a linear combination of IGSF8 and ITGA5 based on logistic regression analysis, we achieved a sensitivity of 80% with 99.8% specificity and a positive predictive value of 13.8%. Importantly, these exo-proteins also can accurately discriminate between ovarian and 12 types of cancers commonly diagnosed in women. Our studies demonstrate that these lineage-associated exo-biomarkers can detect ovarian cancer with high specificity and sensitivity early and potentially while localized to the FT when patient outcomes are more favorable.
2023-10-09 | PXD036726 | Pride
Project description:High-grade serous ovarian carcinoma (HGSOC) is the most lethal gynecologic neoplasm, with five-year survival rate below 30%. Early disease detection is of utmost importance to improve the cure rate of HGSOC. Liquid biopsies are now becoming a new paradigm to develop novel biomarkers with diagnostic and prognostic purposes. The focus of this study was to detect the levels of circulating miRNAs in tissues and sera from patients with HGSOC and to evaluate their diagnostic value. To this end, an array-based discovery platform, followed by an innovative statistical approach of data normalization, was exploited, to identify miRNA species selectively expressed in serum of patients with HGSOC. Sera from 106 high grade serous ovarian carcinoma (HGSOC) and 24 healthy controls were used for profiling serum microRNA using a modified version of a commercially available microarray, with the aim of identifying differentially expressed microRNA between tumor patients and healthy controls.
2017-01-30 | E-MTAB-4667 | biostudies-arrayexpress
Project description:The paper describes a model on the detection of cancer based on cancer and immune biomarkers.
Created by COPASI 4.25 (Build 207)
This model is described in the article:
Improving cancer detection through combinations of cancer and immune biomarkers: a modelling approach
Raluca Eftimie and and Esraa Hassanein
J Transl Med (2018) 16:73
Abstract:
Background: Early cancer diagnosis is one of the most important challenges of cancer research, since in many can- cers it can lead to cure for patients with early stage diseases. For epithelial ovarian cancer (which is the leading cause of death among gynaecologic malignancies) the classical detection approach is based on measurements of CA-125 biomarker. However, the poor sensitivity and specificity of this biomarker impacts the detection of early-stage cancers.
Methods: Here we use a computational approach to investigate the effect of combining multiple biomarkers for ovarian cancer (e.g., CA-125 and IL-7), to improve early cancer detection.
Results: We show that this combined biomarkers approach could lead indeed to earlier cancer detection. However, the immune response (which influences the level of secreted IL-7 biomarker) plays an important role in improving and/or delaying cancer detection. Moreover, the detection level of IL-7 immune biomarker could be in a range that would not allow to distinguish between a healthy state and a cancerous state. In this case, the construction of solu- tion diagrams in the space generated by the IL-7 and CA-125 biomarkers could allow us predict the long-term evolu- tion of cancer biomarkers, thus allowing us to make predictions on cancer detection times.
Conclusions: Combining cancer and immune biomarkers could improve cancer detection times, and any predic- tions that could be made (at least through the use of CA-125/IL-7 biomarkers) are patient specific.
Keywords: Ovarian cancer, Mathematical model, CA-125 biomarker, IL-7 biomarker, Cancer detection times
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2024-09-02 | BIOMD0000000741 | BioModels
Project description:High-grade serous ovarian cancer (HGSOC) represents the major histological type of ovarian cancer (OC), and lack of effective screening tools and early detection methods significantly contributes to the poor prognosis of HGSOC. Currently, there is no reliable diagnostic biomarkers for HGSOC. In this study, we performed liquid chromatography data-independent acquisition tandem-mass spectrometry on depleted serum samples from 26 HGSOC cases and 24 healthy controls (HCs) to discover potential HGSOC diagnostic biomarkers. A total of 1,847 proteins were identified across all samples, among which 116 proteins showed differential expressions between HGSOC patients and HCs. Network modeling showed activations of coagulation and complement cascades, platelet activation and aggregation, NET formation, TLR4, IGF, and TGF-β signaling, and suppression of lipoprotein assembly and FcγR activation in HGSOC. Based on the network model, we prioritized 28 biomarker candidates, and validated 18 of them using targeted MS assays in an independent cohort. Predictive modeling showed a sensitivity of 1 and specificity of 0.91 in the validation cohort. Finally, in vitro functional assays on four potential biomarkers (FGA, VWF, ARHGDIB, and SERPINF2) suggested that they may play an important role in cancer cell proliferation and migration in HGSOC.
2022-08-11 | PXD033169 | Pride
Project description:Identification and validation of potential prognostic biomarkers in older ovarian cancer patients with high-grade serous adenocarcinoma (HGSC)
2020-03-01 | GSE126308 | GEO
Project description:We aimed to discover and validate a panel of serum biomarkers for high grade serous ovarian cancer (HGSOC) using our lectin-magnetic bead array-coupled proteomics platform. Serum from age-matched women with HGSOC, benign tumours or healthy controls were analysed in discovery (UKCTOCS, n=30 and UKOPS, n=30) and validation (Australian Ovarian Cancer Study, n=95) cohorts using shotgun and targeted proteomics, respectively. A 7-lectin discovery screen shortlisted 60 candidate proteins and 3 lectins for validation, which revealed elevated levels of AAL, SNA or STL-binding FIBB, CO9, ITIH3, HPT, A1AT, AACT in HGSOC, while IBP3, A2MG, PON1, CHLE and ALS were reduced. Multimarker panels were developed using generalized regression with lasso estimation and leave-one-out cross-validation. The best performing panel comprised of 13 peptides from Solanum Tuberosum lectin (STL)-binding proteins with 96.3% area under the receiver operating curve, 97.7% specificity and 78.6% sensitivity for distinguishing HGSOC from benign and healthy groups. The peptides robust in cross-validations were from IBP3, KNG1, CO9, THRB, HPTR, HPT, FINC, FA10, GELS. The validated serum biomarkers show promise for early detection of HGSOC and should be further evaluated.
2023-10-24 | PXD032299 | Pride