Sodium-dependent phosphate transporter NaPi2b as a potential predictive marker for targeted therapy of ovarian cancer

Abstract

The high mortality rate from ovarian cancer is due to the asymptomatic nature of the course of the disease, which leads to the diagnosis of ovarian cancer in later stages. The sodium-dependent phosphate transporter NaPi2b encoded by SLC34A2 gene is expressed in 80–90% of epithelial ovarian cancers and used as a target for therapeutic antibodies XMT-1536, and XMT-1592, which are derived from MX35 antibodies and used in clinical trials for the treatment of ovarian and lung cancers. In this work, we aimed to evaluate NaPi2b as a molecular marker for diagnostics and predicting the course and outcome of ovarian cancer disease. Quantitative analysis of SLC34A2 gene expression in ovarian tumor tissue was performed at the level of transcription and translation using real-time PCR, droplet digital PCR and Western blot analysis respectively. Statistical analysis was performed taking into account various clinicopathological characteristics of the ovarian cancer patients, including the stage of the disease, the tumor grade, the applying of neoadjuvant chemotherapy and the presence of ascites. In this work, we demonstrated that the expression of the human NaPi2b (hNaPi2b) transporter is downregulated in the tumors of patients receiving neoadjuvant therapy and during the development of disease. The data suggest that the level of expression of the SLC34A2 gene can serve as a potential marker for the monitoring and predicting responses to neoadjuvant and targeted therapy in patients with ovarian cancer.

Machine learning-based analysis of cancer cell-derived vesicular proteins revealed significant tumor-specificity and predictive potential of extracellular vesicles for cell invasion and proliferation – A meta-analysis

“…In addition to the above examples, the results of our enrichment study are supported by further literature on leukemia [63], melanoma [64], lung [65,66] and ovarian cancer [67,68].…”

Toward a Topology-Based Therapeutic Design of Membrane Proteins: Validation of NaPi2b Topology in Live Ovarian Cancer Cells

“…Thus, NaPi2b represents a promising target for antitumor therapy due to its predominant membrane localization, existence of potential cancer-specific epitope, and increased expression in several tumors. However, we have shown recently that neo-adjuvant therapy with carboplatin and paclitaxel reduces the protein expression of the NaPi2b transporter in tumors of ovarian carcinoma, which calls into question the use of correspondent antibodies for ovarian cancer patients' treatment (Nurgalieva et al, 2021).…”

Selected markers of ovarian cancer and their relation to targeted therapy (Review)

“…The expression of this gene was found to be downregulated in patients receiving neoadjuvant chemotherapy. Thus, expression of this gene may be a marker for predicting response to such therapy ( 8 ).…”