Expression of the Receptor for Hyaluronic Acid-Mediated Motility (RHAMM) in Endometrial Cancer is Associated With Adverse Histologic Parameters and Tumor Progression.
Expression of the Receptor for Hyaluronic Acid-Mediated Motility (RHAMM) in Endometrial Cancer is Associated With Adverse Histologic Parameters and Tumor Progression.
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DOI：
10.1097/pai.0000000000000763
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发表时间：
2020-07
期刊：
影响因子：
--
通讯作者：
Du YN
中科院分区：
文献类型：
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作者：
Schatz-Siemers N;Chen YT;Chen Z;Wang D;Ellenson LH;Du YN
子宫内膜癌是世界范围内最常见的妇科恶性肿瘤之一。自1971年以来，只有两种药物被食品和药物管理局批准用于子宫内膜癌。需要确定治疗晚期子宫内膜癌的分子靶点。透明质酸介导的运动受体（RHAMM）在各种类型的癌症中上调。本研究旨在探讨RHAMM在子宫内膜癌中表达的临床意义。对225例子宫内膜癌（包括浆液性和浆液性）和8例正常子宫内膜进行了RHAMM蛋白水平的研究。还查询了公开可用的癌症基因组图谱（TCGA）数据库中子宫内膜癌中的RHAMM mRNA表达。RHAMM蛋白在子宫内膜癌中表达增加，而在正常子宫内膜中无表达或弱表达。RHAMM表达与肿瘤分级呈正相关。与侵袭性相对较低的子宫内膜样癌相比，子宫内膜浆液性癌（高级别、侵袭性类型的子宫内膜癌）中RHAMM的表达显着增加。RHAMM表达也与淋巴管浸润的存在相关。RHAMM mRNA表达与TCGA队列中生存率降低相关。因此，子宫内膜癌中RHAMM表达的增加与高级别肿瘤相关，并指示更具侵袭性的行为。这些发现表明RHAMM作为子宫内膜癌的预后因素，并作为一个潜在的治疗目标，在未来的研究中晚期子宫内膜癌。
Endometrial cancer is one of the most common gynecologic malignancies worldwide. Only two agents have been approved by Food and Drug Administration for endometrial cancer since 1971. There is a need to identify molecular targets to treat advanced endometrial cancer. The receptor for hyaluronan-mediated motility (RHAMM) is upregulated in various types of cancer. Here, we aimed to determine the clinical significance of RHAMM expression in endometrial cancer. Two hundred and twenty-five cases of endometrial cancer, including serous and endometrioid types, and 8 cases of normal endometrium were used for studying RHAMM protein levels. Publically available The Cancer Genome Atlas (TCGA) database was also queried for RHAMM mRNA expression in endometrial cancer. Increased expression of RHAMM protein was seen in endometrial cancer compared with no or weak expression in normal endometrium. RHAMM expression positively correlated with tumor grade. RHAMM expression was significantly increased in endometrial serous carcinomas, which are high-grade, aggressive types of endometrial cancer, compared with the relatively less aggressive endometrioid carcinomas. RHAMM expression also correlated with the presence of lymphovascular invasion. RHAMM mRNA expression correlated with decreased survival in the TCGA cohort. Therefore, increased RHAMM expression in endometrial cancer is associated with high-grade tumors and is indicative of more aggressive behavior. These findings suggest RHAMM as a prognostic factor in endometrial cancer and as a potential therapeutic target in advanced endometrial cancer for future studies.