High expression of AGBL2 is a novel prognostic factor of adverse outcome in patients with ovarian carcinoma

Abstract

The putative oncogenic role of ATP/GTP binding protein like 2 (AGBL2) in catalyzing α-tubulin detyrosination has recently been characterized in cancer. However, the status of AGBL2 expression in ovarian cancer and its potential clinical and prognostic significance remain unclear. In the present study, immunohistochemistry staining investigated the protein expression level of AGBL2 in paraffin-embedded pathological specimens from 30 normal ovaries, 35 ovarian cystadenomas, 38 borderline ovarian tumors and 165 invasive ovarian carcinomas. The association between AGBL2 expression and clinicopathological characteristics of patients was evaluated using the χ2 test or Fisher's exact test. The survival status of patients was assessed by receiver-operator curve analysis. The results demonstrated that high expression of AGBL2 was observed in 9% of cystadenomas cases, 21% of borderline tumors cases and 38% of ovarian carcinomas cases; however AGBL2 expression was not high in normal ovarian tissues (P<0.01). Furthermore, the results demonstrated that high expression of AGBL2 was associated with tumor histological grade, advanced pT/pN/pM and cancer stage according to the International Federation of Gynecology and Obstetrics (P<0.05). Following univariate survival analysis of the ovarian carcinoma groups, high expression of AGBL2 was significantly associated with shorter patient survival (P<0.001). In addition, multivariate analysis revealed that AGBL2 could be identified as a potential independent prognostic factor for overall survival in patients with ovarian carcinoma (P=0.004). Furthermore, the results demonstrated that AGBL2 expression was significantly associated with the expression of immunity related GTPase M (IRGM) (P=0.013) and LC3A/B (P=0.004). IRGM expression level was also significantly associated with LC3A/B expression level (P=0.023). These findings demonstrated that AGBL2 expression was high in ovarian carcinomas, which suggested that AGBL2 may participate in the acquisition of an aggressive phenotype and may therefore serve as an independent prognostic molecular marker.