Overexpression of SLC12A5 is associated with tumor progression and poor survival in ovarian carcinoma

Abstract

Introduction The solute carrier family 12 member 5 (SLC12A5) gene is playing a putative oncogenic role in colorectal carcinoma. However, the status of SLC12A5 amplification and expression in ovarian carcinoma and its potential clinical and/or prognostic significance has not yet been investigated. Methods In the present study, semi-quantitative staining and fluorescence in situ hybridization were used to investigate SLC12A5 protein expression and gene amplification levels. Samples were obtained from archival, formalin-fixed, paraffin-embedded pathological specimens consisting of 30 normal ovaries, 30 ovarian cystadenomas, 30 borderline ovarian tumors, and 147 invasive ovarian carcinomas. SLC12A5 immunohistochemical staining results, pathological parameters, and patient prognosis were then evaluated using various statistical models. Patient survival rate was also assessed using receiver-operator curve analysis. Results Our results revealed no SLC12A5 protein overexpression in normal ovaries. However, 7% of cystadenomas had SLC12A5 protein overexpression along with 17% of borderline tumors and 37% of ovarian carcinomas (P<0.01). Amplification of SLC12A5 was detected in 10.3% of ovarian carcinomas. Further correlational analyses showed that SLC12A5 protein overexpression in ovarian carcinomas was significantly associated with ascending histological grade, pT/pN/pM status, as well as FIGO stage (P<0.05). A subsequent univariate survival analysis of our ovarian carcinoma cohorts resulted in a significant association between SLC12A5 protein overexpression and decreased patient survival (44.3 and 85.9 months for high and low SLC12A5 protein expression, respectively; P<0.001). Importantly, additional multivariate analysis revealed that SLC12A5 protein expression was a significant, independent prognostic factor for overall survival in ovarian carcinoma patients (P=0.003). Conclusions Collectively, these findings support the conclusion that SLC12A5 protein overexpression could indicate an invasive and/or aggressive phenotype of ovarian carcinoma. Future work will need to investigate whether SLC12A5 protein can serve as an independent prognostic molecular marker in patients with ovarian carcinoma.