Abstract

Ovarian cancer (OC) is commonly diagnosed at advanced stage when prognosis is poor. Consequently, there is an urgent clinical need to identify novel biomarkers for early detection to improve survival. We examined the diagnostic value of the calcium phospholipid binding protein annexin A2 (ANXA2), which plays an important role in OC metastasis. Annexin A2 plasma levels in patients with high grade serous OC (n = 105), benign ovarian lesions (n = 55) and healthy controls (n = 143) were measured by ELISA. Annexin A2 levels were found to be significantly increased in patients with stage I (p < 0.0001) and stage IA (p = 0.0027) OC when compared to healthy controls. In the logistic regression models followed by receiver operating characteristics (ROC) curve analyses, plasma annexin A2 showed 46.7% sensitivity at 99.6% specificity in distinguishing stage IA OC patients from healthy controls and 75% sensitivity at 65.5% specificity in the diagnosis of stage IA versus benign ovarian tumors. In the diagnosis of stage IA OC versus normal controls, the combination of plasma annexin A2 and CA125 showed 80% sensitivity at 99.6% specificity (AUC = 0.970) which was significantly higher than for CA125 (53.3% sensitivity at 99.6% specificity; AUC = 0.891) alone. The diagnostic accuracy in distinguishing stage IA OC from benign ovarian disease when combining annexin A2 and CA125 (71.4% accuracy at 100% sensitivity) was almost twice as high compared to CA125 (37.1% accuracy at 100% sensitivity) alone. In conclusion, annexin A2 in combination with CA125 has potential as a biomarker for the early detection of OC and to predict malignancy in patients with ovarian lesions, warranting further investigations.

Highlights

  • Ovarian cancer (OC) is the gynecological malignancy with the highest mortality and accounts for an estimated 152,000 deaths worldwide each year [1]

  • Plasma annexin A2 levels were significantly elevated in patients with FIGO stage I (1A-IC) (2.42-fold increase, p < 0.0001) and IA (2.51-fold increase, p = 0.0027) OC compared to healthy controls

  • No significant difference was observed between plasma annexin A2 in patients with stage IA (2.07-fold increase, p = 0.13), stage II (1.81-fold increase, p = 0.08) or stage III/IV OC (1.04-fold increase, p = 0.10) versus benign ovarian lesions

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Summary

Introduction

Ovarian cancer (OC) is the gynecological malignancy with the highest mortality and accounts for an estimated 152,000 deaths worldwide each year [1]. The high mortality of OC is caused by the asymptomatic nature of early disease, resulting in over 70% of patients being diagnosed at advanced stage when the cancer has metastasized (International Federation of Gynecology and Obstetrics (FIGO) stage III and IV). Prognosis at this stage is poor and 5-year survival is only about 30%. Early detection is the most effective way of improving OC survival. Currently no effective early detection tests are available and population screening is not possible

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