Abstract
Ovarian cancer (OvCa) is one of the leading causes of death due to its high metastasis rate to the peritoneum. Recurrent peritoneal tumors also develop despite the use of conventional platinum-based chemotherapies. Therefore, it is still important to explore the factors associated with peritoneal metastasis, as these predict the prognosis of patients with OvCa. In this study, we investigated the function of microphthalmia-associated transcription factor (MITF), which contributes to the development of melanoma, in epithelial ovarian cancer (OvCa). High MITF expression was significantly associated with a poor prognosis in OvCa. Notably, MITF contributed to the motility and invasion of OvCa cells, and specifically with their peri-mesothelial migration. In addition, MITF-positive cells expressed the melanoma cell adhesion molecule (MCAM/CD146), which was initially identified as a marker of melanoma progression and metastasis, and MCAM expression was regulated by MITF. MCAM was also identified as a significant prognostic factor for poor progression-free survival in patients with OvCa. Collectively, our results suggest that MITF is a novel therapeutic target that potentially promotes peritoneal metastasis of OvCa.
Highlights
More than half of all patients with ovarian cancer (OvCa) are diagnosed at an advanced stage, contributing to the fact that OvCa is the leading cause of death in the field of gynecology [1,2,3]
We investigated the function of microphthalmia-associated transcription factor (MITF), which contributes to the development of melanoma, in epithelial ovarian cancer (OvCa)
The OvCa expression database suggested that tumors with a high expression of MITF were associated with significantly worse prognosis than those with low expression, in all patients and in those with stage III disease (Figure 1D)
Summary
More than half of all patients with ovarian cancer (OvCa) are diagnosed at an advanced stage, contributing to the fact that OvCa is the leading cause of death in the field of gynecology [1,2,3]. Peritoneal dissemination, which is one of the most common types of metastasis in the abdominal cavity, is frequently observed in patients with advanced OvCa [4,5]. Primary peritoneal carcinoma and advanced OvCa are similar in having peritoneal dissemination and are treated . Even when primary tumors are optimally resected, recurrent tumors frequently emerge in the peritoneum despite the use of conventional platinum-based chemotherapies [7,8] and the estimated median progression-free survival (PFS) is approximately 12–18 months [9]. It remains important to explore the factors associated with the peritoneal metastasis of OvCa, as these can serve as biomarkers that predict patient prognosis, and as therapeutic targets in refractory OvCa
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