Increased expression of Na+/H+ exchanger isoform 1 predicts tumor aggressiveness and unfavorable prognosis in epithelial ovarian cancer

摘要

Na⁺/H⁺ exchanger isoform 1 (NHE1), which is a regulator of intracellular and extracellular pH via ion exchange, has been demonstrated to serve an important role in cell differentiation, migration and invasion in solid tumors and hematological malignancies. However, the potential role of NHE1 in epithelial ovarian cancer (EOC) remains unclear. In the present study, the expression pattern and the prognostic value of NHE1 were investigated in EOC. EOC tissues, non-cancerous tumors and normal ovarian tissues were collected, and the expression levels of NHE1 were determined using the reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. The expression pattern of NHE1 was also evaluated in ovarian cancer cell lines using western blotting and immunofluorescence. In addition, the association between the NHE1 expression pattern and the clinicopathological features and the clinical prognosis of patients with EOC was also analyzed. The expression levels of NHE1 were identified to be significantly increased in EOC tissues compared with non-cancerous tumors and normal ovarian tissues (P<0.05). Furthermore, the increased expression of NHE1 was associated with an advanced International Federation of Gynecology and Obstetrics stage (FIGO III–IV; P<0.001) and the presence of high-grade carcinoma (grades 2–3, P<0.001). Overexpressed NHE1 was identified as a risk factor of shorter PFS (P<0.001) and OS (P<0.001). A multivariate Cox's regression analysis revealed that NHE1 was an independent prognostic factor for the prediction of the outcome of patients with EOC. NHE1 may, therefore, serve as a potential therapeutic target to inhibit tumor aggressiveness.