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Autoantibody biomarkers identified by proteomics methods distinguish ovarian cancer from non-ovarian cancer with various CA-125 levels.

ABSTRACT: CA-125 has been a valuable marker for detecting ovarian cancer, however, it is not sensitive enough to detect early-stage disease and not specific to ovarian cancer. The purpose of our study was to identify autoantibody markers that are specific to ovarian cancer regardless of CA-125 levels.Top-down and iTRAQ quantitative proteomics methods were used to identify high-frequency autoantibodies in ovarian cancer. Protein microarrays comprising the recombinant autoantigens were screened using serum samples from various stages of ovarian cancer with diverse levels of CA-125 as well as benign and healthy controls. ROC curve and dot blot analyses were performed to validate the sensitivity and specificity of the autoantibody markers.The proteomics methodologies identified more than 60 potential high-frequency autoantibodies in ovarian cancer. Individual serum samples from ovarian cancer stages I-IV compared to control samples that were screened on a microarray containing native recombinant autoantigens revealed a panel of stage I high-frequency autoantibodies. Preliminary ROC curve and dot blot analyses performed with the ovarian cancer samples showed higher specificity and sensitivity as compared to CA-125. Three autoantibody markers exhibited higher specificity in various stages of ovarian cancer with low and normal CA-125 levels.Proteomics technologies are suitable for the identification of protein biomarkers and also the identification of autoantibody biomarkers when combined with protein microarray screening. Using native recombinant autoantigen arrays to screen autoantibody markers, it is possible to identify markers with higher sensitivity and specificity than CA-125 that are relevant to early detection of ovarian cancer.

SUBMITTER: Karabudak AA

PROVIDER: S-EPMC3832954 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Autoantibody biomarkers identified by proteomics methods distinguish ovarian cancer from non-ovarian cancer with various CA-125 levels.

Karabudak Aykan A AA Hafner Julie J Shetty Vivekananda V Chen Songming S Secord Angeles Alvarez AA Morse Michael A MA Philip Ramila R

Journal of cancer research and clinical oncology 20130903 10

<h4>Purpose</h4>CA-125 has been a valuable marker for detecting ovarian cancer, however, it is not sensitive enough to detect early-stage disease and not specific to ovarian cancer. The purpose of our study was to identify autoantibody markers that are specific to ovarian cancer regardless of CA-125 levels.<h4>Methods</h4>Top-down and iTRAQ quantitative proteomics methods were used to identify high-frequency autoantibodies in ovarian cancer. Protein microarrays comprising the recombinant autoant ...[more]

PMID: 23999876

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Project description:A 2009 randomized clinical trial demonstrated that using cancer antigen 125 (CA-125) tests for routine surveillance in ovarian cancer increases the use of chemotherapy and decreases patients' quality of life without improving survival, compared with clinical observation. The Society of Gynecologic Oncology guidelines categorize CA-125 testing as optional and discourage the use of radiographic imaging for routine surveillance. To date, few studies have examined the use of CA-125 tests in clinical practice.To examine the use of CA-125 tests and computed tomographic (CT) scans in clinical practice before and after the 2009 randomized clinical trial and to estimate the economic effect of surveillance testing.A prospective cohort of 1241 women with ovarian cancer in clinical remission after completion of primary cytoreductive surgery and chemotherapy at 6 National Cancer Institute-designated cancer centers between January 1, 2004, and December 31, 2011, was followed up through December 31, 2012, to study the use of CA-125 tests and CT scans before and after 2009. Data analysis was conducted from April 9, 2014, to March 28, 2016.The use of CA-125 tests and CT scans before and after 2009. Secondary outcomes included the time from CA-125 markers doubling to retreatment among women who experienced a rise in CA-125 markers before and after 2009, and the costs associated with surveillance testing using 2015 Medicare reimbursement rates.Among 1241 women (mean [SD] age 59 [12] years; 1112 white [89.6%]), the use of CA-125 testing and CT scans was similar during the study period. During 12 months of surveillance, the cumulative incidence of patients undergoing 3 or more CA-125 tests was 86% in 2004-2009 vs 91% in 2010-2012 (P?=?.95), and the cumulative incidence of patients undergoing more than 1 CT scan was 81% in 2004-2009 vs 78% in 2010-2012 (P?=?.50). Among women whose CA-125 markers doubled (n?=?511), there was no significant difference in the time to retreatment with chemotherapy before and after 2009 (median, 2.8 vs 3.5 months; P?=?.40). During a 12-month period, there was a mean of 4.6 CA-125 tests and 1.7 CT scans performed per patient, resulting in a US population surveillance cost estimate of $1?999?029 per year for CA-125 tests alone and $16?194?647 per year with CT scans added.CA-125 tests and CT scans are still routinely used for surveillance testing in patients with ovarian cancer, although their benefit has not been proven and their use may have significant implications for patients' quality of life as well as costs.

Project description:UnlabelledBackgroundThere is no consensus regarding the management of ovarian cancer patients, who have shown complete clinical response (CCR) to primary therapy and have rising cancer antigen CA-125 levels but have no symptoms of recurrent disease. The present study aims to determine whether follow-up CA-125 levels can be used to identify the need for imaging studies and secondary cytoreductive surgery (CRS).MethodsWe identified 410 ovarian cancer patients treated at The University of Texas MD Anderson Cancer Center between 1984 and 2011. These patients had shown CCR to primary therapy. Follow-up was conducted based on the surveillance protocol of the MD Anderson Cancer Center. We used the Cox proportional hazards model and log-rank test to assess the associations between the follow-up CA-125 levels and secondary CRS and survival duration.ResultsThe CA-125 level of 1.68?×?nadir was defined as the indicator of recurrent disease (p?<?0.001). The specificity and sensitivity of this criterion were 82.9% and 85.6%, respectively, and the median lead-time of the CA-125 biochemical progression prior to clinically-defined relapse was 31?days (ranging from 1 to 391?days). The median number of the negative imaging studies for the clinical relapse findings in patients with a CA-125 level of?<?1.68?×?nadir was 3 (ranging from 0 to 24 times). The increase of CA-125 level at relapse was an independent predictor of overall and progression free survival in patients who had shown CCR to primary therapy (p?=?0.04 and 0.02 respectively). The overall and progression free survival durations in patients with a CA-125 level???1.68?×?nadir at relapse (69.4 and 13.8?months) were longer than those with a CA-125 level?>?1.68?×?nadir at relapse (55.7 and 10.4?months; p?=?0.04 and 0.01, respectively). The overall and progression free survival duration of patients with asymptomatic relapse and underwent a secondary CRS was longer than that of patients with symptomatic relapse (p?=?0.02 and 0.04 respectively).ConclusionsThe increase of serum CA-125 levels is an early warning of clinical relapse in ovarian cancer. Using CA-125 levels in guiding the treatment of patients with asymptomatic recurrent ovarian cancer, who have shown CCR to primary therapy, can facilitate optimal secondary CRS and extend the survival duration of the patients.

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Autoantibody biomarkers identified by proteomics methods distinguish ovarian cancer from non-ovarian cancer with various CA-125 levels.

Publications

Autoantibody biomarkers identified by proteomics methods distinguish ovarian cancer from non-ovarian cancer with various CA-125 levels.

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