Diagnostic Value of Plasma Annexin A2 in Early-Stage High-Grade Serous Ovarian Cancer

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.

Inflammatory serum factors from aortic valve stenosis patients modulate sex differences in valvular myofibroblast activation and osteoblast-like differentiation

“…As an initial validation, male and female VICs were isolated from porcine aortic valve leaflets, seeded on TCPS, and cultured for 48 hours with physiologically relevant concentrations of annexin A2 and cystatin C. [37][38][39][40] We hypothesized that we would observe increased myofibroblast activation in female VICs and increased osteoblast-like differentiation in male VICs in response to annexin A2 and cystatin C. However, aside from an increase in male VIC RUNX2 nuclear localization when cultured with high doses of cystatin C, annexin A2 and cystatin C had a minimal impact on VIC myofibroblast activation and osteoblast-like differentiation (ESI Fig. 4 †).…”

Multi-modal Profiling of the Extracellular Matrix of Human Fallopian Tubes and Serous Tubal Intraepithelial Carcinomas

“…39 Annexin A2 has also been shown recently to have potential as a biomarker for ovarian cancer, as levels in the blood were elevated in patients with stage I or II disease relative to healthy controls and benign tumors. 40 PAI-1 levels have been shown to correlate with peritoneal metastasis and a worse prognosis in HGSOC. 41 LAMA5 has been shown to be expressed in endometrioid ovarian cancer 42 and ovarian clear cell carcinoma, 43 but to our knowledge has not been described in HGSOC.…”

Annexins A2 and A5 are potential early biomarkers of hepatocarcinogenesis

“…Based on a well-accepted animal model of diethylnitrosamine-induced cirrhosis-HCC and using available data in the LIHC-TCGA RNA-seq database, we have revealed the tissue and plasma status of five annexin family members during hepatocarcinogenesis and determined their usefulness as potential noninvasive markers for the diagnosis of HCC early stages. Some members of the annexins have been identified as circulating biomarkers in several types of cancer 22 , 24 , 26 , 31 , 32 …”

“…ANXA2 is the member of the annexin family most studied as a circulating biomarker 14 , 22 , 31 , 32 or tumor marker 39 in various types of cancer; moreover, this protein has been widely considered a circulating biomarker for identifying early stages of liver cancer 14 , 21 , 22 , 24 . Our results demonstrate that ANXA2 increased at both mRNA and protein levels in the liver tissue as early as 12 weeks and persisted until 22 weeks during hepatocarcinogenesis (Figs.…”