Prognostic Significance of Increased Expression of Annexin A10 (ANXA10) in Serous Epithelial Ovarian Cancer

Abstract

BACKGROUND Epithelial ovarian cancer (EOC) is a gynecological malignancy that is associated with high mortality. Annexin A10 (ANXA10) is variably expressed in several types of human malignancy, but its role and clinical significance in EOC remain unknown. This study aimed to investigate the role of ANXA10 in EOC cells in vitro and to study the association between the protein expression levels of the ANXA10 in tumor tissue from patients with serous EOC and clinical outcome. MATERIAL AND METHODS The expression of ANXA10 was studied in 118 cases of serous EOC and in the ovarian cancer cell lines, SKOV-3, HO9810, HO8910PM, and OVCAR3 with immunohistochemistry and Western blot. Correlation between ANXA10 expression and clinicopathological variables and patient outcome were evaluated, including with Kaplan-Meier survival curves, univariate analysis with the log-rank test, and the multivariate analysis with the Cox-regression model. RESULTS ANXA10 was expressed by cells in the ovarian cancer cell lines. Patients with low expression and high expression of ANXA10 were 61.86% (73/118) and 38.14% (45/118), respectively. High expression of ANXA10 was correlated with poor response to chemotherapy (P=0.034), the presence of lymphatic invasion (P=0.043), and the International Federation of Gynecology and Obstetrics (FIGO) advanced stage (P=0.033), which were all associated with lower survival rates of serous EOC. Increased expression of ANXA10 was identified as an independent prognostic biomarker of serous EOC (HR=1.73; 95% CI, 1.01-2.98; P=0.046). CONCLUSIONS Increased expression of ANXA10 was an independent prognostic marker in patients with serous EOC.

Figure 1

Expression of Annexin A10 (ANXA10) in tissue samples from patients with serous epithelial ovarian cancer (EOC) and ovarian cancer cell lines. (A, B) Photomicrographs of the light microscopy findings. Upper panel, the representative images of low expression (A) and high expression (B) of ANXA10. Lower panel, the magnified images of the corresponding figure. Scale bar: 100 μm. The total score of (A) was staining score (1) × positive score (2)=2, while the total score of (B) was staining score (3) × positive score (4)=12. (C) The expressions of ANXA10 in different EOC cell lines SKOV-3, HO9810, HO8910PM and OVCAR3 were detected with Western blot.

Figure 2

The prognostic roles of Annexin A10 (ANXA10), lymphatic invasion, response to chemotherapy, and the International Federation of Gynecology and Obstetrics (FIGO) stage in 118 patients with serous epithelial ovarian cancer (EOC). (A–D) The overall survival curves of patients with serous EOC were stratified with factors including ANXA10 (A), lymph invasion (B), response to chemotherapy (C) and FIGO stage (D). Patients with high expression levels of ANXA10, negative lymphatic invasion, poor response to chemotherapy and advanced FIGO stage had a worse prognosis and reduced overall survival.