Dataset Information

Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer.

ABSTRACT:

Background

CA125 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.

Methods

In 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.

Results

Nine 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.

Conclusion

Using 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.

SUBMITTER: Mukama T

PROVIDER: S-EPMC9042845 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer.

Mukama Trasias T Fortner Renée Turzanski RT Katzke Verena V Hynes Lucas Cory LC Petrera Agnese A Hauck Stefanie M SM Johnson Theron T Schulze Matthias M Schiborn Catarina C Rostgaard-Hansen Agnetha Linn AL Tjønneland Anne A Overvad Kim K Pérez María José Sánchez MJS Crous-Bou Marta M Chirlaque María-Dolores MD Amiano Pilar P Ardanaz Eva E Watts Eleanor L EL Travis Ruth C RC Sacerdote Carlotta C Grioni Sara S Masala Giovanna G Signoriello Simona S Tumino Rosario R Gram Inger T IT Sandanger Torkjel M TM Sartor Hanna H Lundin Eva E Idahl Annika A Heath Alicia K AK Dossus Laure L Weiderpass Elisabete E Kaaks Rudolf R

British journal of cancer 20220114 9

<h4>Background</h4>CA125 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.<h4>Methods</h4>In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood samp ...[more]

PMID: 35031764

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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.

Dataset Information

Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer.

Background

Methods

Results

Conclusion

Publications

Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer.

Similar Datasets

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