Abstract

CA125 as a biomarker of ovarian cancer is ineffective for the general population. The aim of this study was to evaluate multiplexed bead-based immunoassay of multiple ovarian cancer-associated biomarkers such as transthyretin and apolipoprotein A1, together with CA125, to improve the identification and evaluation of prognosis of ovarian cancer. We measured the serum levels of CA125, transthyretin, and apolipoprotein A1 from the serum of 61 healthy individuals, 84 patients with benign ovarian disease, and 118 patients with ovarian cancer using a multiplex liquid assay system, Luminex 100. The results were then analyzed according to healthy and/or benign versus ovarian cancer subjects. When CA125 was combined with the other biomarkers, the overall sensitivity and specificity were significantly improved in the ROC curve, which showed 95% and 97% sensitivity and specificity, respectively. At 95% specificity for all stages the sensitivity increased to 95.5% compared to 67% for CA125 alone. For stage I+II, the sensitivity increased from 30% for CA125 alone to 93.9%. For stage III+IV, the corresponding values were 96.5% and 91.6%, respectively. Also, the three biomarkers were sufficient for maximum separation between noncancer (healthy plus benign group) and stage I+II or all stages (I−IV) of disease. The new combination of transthyretin, and apolipoprotein A1 with CA125 improved both the sensitivity and the specificity of ovarian cancer diagnosis compared with those of individual biomarkers. These findings suggest the benefit of the combination of these markers for the diagnosis of ovarian cancer.

Highlights

  • Ovarian cancer has a higher fatality-to-case ratio than any other gynecologic malignancy, since it tends to be complex by symptoms and misdiagnosed than other diseases, which results in the vast majority of patients with ovarian cancer being diagnosed in advanced metastatic stages [1,2,3]

  • The serum levels of cancer antigen 125 (CA125) was significantly higher in ovarian cancer patients than that in healthy individuals and benign patients, while the levels of transthyretin and apolipoprotein A1 were lower in ovarian cancer patients (Fig. 1A)

  • Conventional ovarian cancer screening tools are ineffective for the general population [3]

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Summary

Introduction

Ovarian cancer has a higher fatality-to-case ratio than any other gynecologic malignancy, since it tends to be complex by symptoms and misdiagnosed than other diseases, which results in the vast majority of patients with ovarian cancer being diagnosed in advanced metastatic stages (stage III/IV) [1,2,3]. CA125 has proven to be a poor diagnostic tumor biomarker because it lacks specificity and sensitivity for early ovarian cancer (only 23% in stage I ovarian cancer, in contrast to more than 80% in advanced ovarian cancer) [11]. It is elevated above reference levels in only 50% of clinically detectable early stage disease, and is not infrequently elevated in patients with benign ovarian diseases [12,13]. Because the measurement of serum concentration of each putative biomarker with individual ELISAs requires considerable time, cost, and sample volumes, new methods or technologies for multiplexing must be developed

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