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Circulating biomarkers for detection of ovarian cancer and predicting cancer outcomes.

ABSTRACT: BACKGROUND: Securing a diagnosis of ovarian cancer and establishing means to predict outcomes to therapeutics remain formidable clinical challenges. Early diagnosis is particularly important since survival rates are markedly improved if tumour is detected early. METHODS: Comprehensive miRNA profiles were generated on presurgical plasma samples from 42 women with confirmed serous epithelial ovarian cancer, 36 women diagnosed with a benign neoplasm, and 23 comparably age-matched women with no known pelvic mass. RESULTS: Twenty-two miRNAs were differentially expressed between healthy controls and the ovarian cancer group (P<0.05), while a six miRNA profile subset distinguished presurgical plasma from benign and ovarian cancer patients. There were also significant differences in miRNA profiles in presurgical plasma from women diagnosed with ovarian cancer who had short overall survival when compared to women with long overall survival (P<0.05). CONCLUSION: Our preliminary data support the utility of circulating plasma miRNAs to distinguish women with ovarian cancer from those with a benign mass and identify women likely to benefit from currently available treatment for serous epithelial ovarian cancer from those who may not.

SUBMITTER: Shapira I

PROVIDER: S-EPMC3929876 | biostudies-other | 2014 Feb

REPOSITORIES: biostudies-other

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Circulating biomarkers for detection of ovarian cancer and predicting cancer outcomes.

Shapira I I Oswald M M Lovecchio J J Khalili H H Menzin A A Whyte J J Dos Santos L L Liang S S Bhuiya T T Keogh M M Mason C C Sultan K K Budman D D Gregersen P K PK Lee A T AT

British journal of cancer 20131224 4

<h4>Background</h4>Securing a diagnosis of ovarian cancer and establishing means to predict outcomes to therapeutics remain formidable clinical challenges. Early diagnosis is particularly important since survival rates are markedly improved if tumour is detected early.<h4>Methods</h4>Comprehensive miRNA profiles were generated on presurgical plasma samples from 42 women with confirmed serous epithelial ovarian cancer, 36 women diagnosed with a benign neoplasm, and 23 comparably age-matched women ...[more]

PMID: 24366298

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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.

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Circulating biomarkers for detection of ovarian cancer and predicting cancer outcomes.

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Circulating biomarkers for detection of ovarian cancer and predicting cancer outcomes.

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