Department of Obstetrics and Gynecology, Kyung Hee University Hospital at Gangdong, Seoul, Republic of Korea.
Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Cancer Genomics Proteomics. 2022 Nov-Dec;19(6):692-702. doi: 10.21873/cgp.20352.
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.
跨膜 emp24 结构域蛋白 9（TMED9）属于 TMED/p24 家族，该家族可将蛋白质和脂质运输、修饰和包装到小泡中，以递送到特定位置，在通过内质网-高尔基体货物途径的固有免疫信号中非常重要。TMED9 与多种癌症类型有关；然而，其在卵巢上皮性癌（EOC）中的作用尚不清楚。在本研究中，我们旨在阐明 TMED9 在 EOC 中的作用和临床意义。
使用 RNA 测序和免疫组织化学数据评估 TMED9 的 mRNA 和蛋白水平及其与 EOC 临床病理特征的关联。还进行了功能研究，以评估 TMED9 在 EOC 细胞系中的致瘤作用。
与正常卵巢上皮相比，EOC 中 TMED9 的 mRNA 表达上调。TMED9 蛋白表达在从正常卵巢上皮到 EOC 的进展中增加（p<0.001）。此外，TMED9 的高表达与 EOC 的晚期分期、浆液细胞类型和组织学分级差相关，并对无病生存和总生存均具有独立的预后意义。进一步的功能研究表明，TMED9 敲低可减少 EOC 细胞的迁移、侵袭、细胞增殖和集落形成。
总的来说，我们的研究结果支持将 TMED9 用作有价值的预后生物标志物，并为 TMED9 作为 EOC 治疗的新策略提供了证据。
