TMED9 Expression Level as a Biomarker of Epithelial Ovarian Cancer Progression and Prognosis.

Abstract

Transmembrane emp24 domain-containing protein 9 (TMED9) belongs to the TMED/p24 family that transports, modifies, and packs proteins and lipids into vesicles for delivery to specific locations and is important in innate immune signaling via the endoplasmic reticulum-Golgi cargo pathway. TMED9 has been implicated in various cancer types; however, its role in epithelial ovarian cancer (EOC) is unclear. In this study, we aimed to elucidate the role and clinical significance of TMED9 in EOC. mRNA and protein levels of TMED9 and their associations with clinicopathological features in EOCs were evaluated using RNA-sequencing and immunohistochemistry data. Functional studies assessing the tumorigenic role of TMED9 in EOC cell lines were also performed. The mRNA expression of TMED9 was up-regulated in EOC compared to that in normal ovarian epithelium. TMED9 protein expression increased in progression from normal ovarian epithelium to EOC (p<0.001). Moreover, high expression of TMED9 was associated with advanced stage, serous cell type and poor histological grade in EOC and demonstrated independent prognostic significance for both disease-free and overall survival. Further functional studies showed that TMED9 knockdown reduced migration, invasion, cell proliferation, and colony formation of EOC cells. Overall, our results support the use of TMED9 as a valuable prognostic biomarker and provide evidence for targeting of TMED9 as a novel strategy for EOC treatment.