Early detection biomarkers for ovarian cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Sarojini S
PROVIDER: S-EPMC3540796 | biostudies-literature | 2012
REPOSITORIES: biostudies-literature
Publications
Early detection biomarkers for ovarian cancer.
Sarojini Sreeja S Tamir Ayala A Lim Heejin H Li Shihong S Zhang Shifang S Goy Andre A Pecora Andrew A Suh K Stephen KS
Journal of oncology 20121223
Despite the widespread use of conventional and contemporary methods to detect ovarian cancer development, ovarian cancer remains a common and commonly fatal gynecological malignancy. The identification and validation of early detection biomarkers highly specific to ovarian cancer, which would permit development of minimally invasive screening methods for detecting early onset of the disease, are urgently needed. Current practices for early detection of ovarian cancer include transvaginal ultraso ...[more]
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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:Ovarian cancer is frequently diagnosed at an advanced stage and a fraction of these patients fail to respond to primary therapy and relapses in 70% of cases. On account of the high recurrence probability and the poor outcomes after recurrence, there is an urgent need to predict progression as early as possible and thus found the strategies to detect and prevent a recurrence. Considering that biomarkers have contributed to the management of ovarian cancer by distinguishing benign and malignant pelvic masses and monitoring response to treatment, in this review, we aim to discuss the latest evidence reported in the literature about the use of biomarkers to detect OC recurrence. In detail, we summarized all the evidence of the most quoted biomarkers like HE4, osteopontin, mesothelin (MSLN), Folate receptor ? (FOLR1), paraneoplastic antigens, miRNA, cancer stem cells (CSCs) and a combination of them to evaluate their role as prognostic biomarkers for ovarian cancer recurrence.
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Project description:More than two-thirds of all women diagnosed with epithelial ovarian cancer (EOC) will die from the disease (>14,000 deaths annually), a fact that has not changed considerably in the last three decades. Although the 5-year survival rates for most other solid tumors have improved steadily, ovarian cancer remains an exception, making it the deadliest of all gynecologic cancers and five times deadlier than breast cancer. When diagnosed early, treatment is more effective, with a 5-year survival rate of up to 90%. Unfortunately, most cases are not detected until after the cancer has spread, resulting in a dismal 5-year survival rate of less than 30%. Current screening methods for ovarian cancer typically use a combination of a pelvic examination, transvaginal ultrasonography, and serum cancer antigen 125 (CA125), but these have made minimal impact on improving mortality. Thus, there is a compelling unmet need to develop new molecular tools that can be used to diagnose early-stage EOC and/or assist in the clinical management of the disease after a diagnosis, given that more than 220,000 women are living with ovarian cancer in the United States and are at risk of recurrence. Here, we discuss the state of advancing liquid-based approaches for improving the early detection of ovarian cancer.See all articles in this Special Collection Honoring Paul F. Engstrom, MD, Champion of Cancer Prevention.
| S-EPMC7080297 | biostudies-literature
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:Early detection of ovarian cancer has the potential to impact mortality. A multimodal screening strategy where rising CA125 values over time, analyzed with the risk of ovarian cancer algorithm (ROCA), triggers transvaginal sonography and possible surgery has high sensitivity and specificity, but still fails to detect the 20% of early-stage cases that do not express CA125. Use of multiple biomarkers could detect cases missed by CA125. We have studied the sensitivity and lead time of a multi-marker panel (CA125, HE4, MMP-7, and CA 72-4) compared with CA125 alone. We used PRoBE design principles to select preclinical longitudinal specimens from 75 women (50 screen-positive, 25 screen-negative) who developed invasive epithelial ovarian cancer (3-5 serial specimens each) and 547 corresponding healthy controls (1-10 serial specimens each) from the ovarian cancer screening trial, UKCTOCS, in a blinded fashion. We measured the multi-marker concentrations in ultra-low serum volumes (16 μL) utilizing multiplexed bead-based immunoassays with low detection limits, high inter- and intra-assay precision, negligible cross-reactivity, and good correlation with standard immunoassays. While, at least one of the complementary biomarkers rose with CA125 in 44% (22/50) of screen-positive cases, there was no advantage in lead time over CA125. Therefore, we developed single-marker longitudinal algorithms (ROCA-like) to determine the presence of a change point to distinguish between the cases and controls. Using these algorithms, at 98% specificity, HE4 and CA72-4 identified 16% (4/25) of screen-negative cases, while MMP-7 identified none. Taken together, HE4 and CA72-4 show promise as complementary biomarkers to CA125 for longitudinal screening.
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Project description:BackgroundCA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer.MethodsIn the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer.ResultsNine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancer-free. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9-18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone.ConclusionUsing pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0-9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125.
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Project description:Autoanitbody Biomarkers for the Early Detection of Serous Ovarian Cancer
| PRJNA316072 | ENA
Project description:Human epididymis protein 4 (HE4) shows promise as a serum marker that complements CA125 in the early detection of epithelial ovarian cancer, either as a first-line screen or as a second-line screen in a multimodal strategy. Incorporation of symptoms in a screening strategy that includes CA125 and HE4 may warrant further research.
| S-EPMC3280618 | biostudies-other
Project description:A panel of biomarkers may improve predictive performance over individual markers. Although many biomarker panels have been described for ovarian cancer, few studies used prediagnostic samples to assess the potential of the panels for early detection. We conducted a multisite systematic evaluation of biomarker panels using prediagnostic serum samples from the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) screening trial. Using a nested case-control design, levels of 28 biomarkers were measured laboratory-blinded in 118 serum samples obtained before cancer diagnosis and 951 serum samples from matched controls. Five predictive models, each containing 6 to 8 biomarkers, were evaluated according to a predetermined analysis plan. Three sequential analyses were conducted: blinded validation of previously established models (step 1); simultaneous split-sample discovery and validation of models (step 2); and exploratory discovery of new models (step 3). Sensitivity, specificity, sensitivity at 98% specificity, and AUC were computed for the models and CA125 alone among 67 cases diagnosed within one year of blood draw and 476 matched controls. In step 1, one model showed comparable performance to CA125, with sensitivity, specificity, and AUC at 69.2%, 96.6%, and 0.892, respectively. Remaining models had poorer performance than CA125 alone. In step 2, we observed a similar pattern. In step 3, a model derived from all 28 markers failed to show improvement over CA125. Thus, biomarker panels discovered in diagnostic samples may not validate in prediagnostic samples; utilizing prediagnostic samples for discovery may be helpful in developing validated early detection panels.
| S-EPMC3057372 | biostudies-literature