Zhang Ran, Jiao Jinwen, Chu Huijun, Yang Hongjuan, Wang Liming, Gao Nana
Qingdao University, Qingdao, Shandong, China.
Department of Gynecology, the Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
Histol Histopathol. 2018 Aug;33(8):859-870. doi: 10.14670/HH-11-986. Epub 2018 Mar 23.
Double primary endometrioid endometrial and ovarian carcinomas (DPEEOCs) are the most common multiple gynecological carcinomas. In recent years, gene sequential comparison analysis has strongly supported the opinion that sporadic double endometrioid endometrial and ovarian cancers (DEEOCs) are clonally related in both primary and metastatic tumors. In order to find more clonal evidence for DPEEOC, we investigated cancer stem cells (CSCs). SOX2 and OCT4 are two common factors in CSCs. MicroRNA (miRNA)-145, a small non-coding RNA, has effects in regulating gene expression and tumorigenesis in CSCs. The aim of this study was to assess the involvements of SOX2, OCT4, and miRNA-145 in the tumorigenesis of DPEEOCs. In our study, twenty DPEEOC patients were chosen. Metastatic DEEOCs and normal endometrial and ovarian tissues were also included. The expression of miRNA-145 was detected by real-time quantitative PCR. Immunohistochemical staining was used to measure the expression of OCT4 and SOX2. The results showed that miRNA-145 expression was lower in DPEEOC endometrial tissues and higher in DPEEOC ovarian tissues compared to the corresponding normal tissues. Both SOX2 and OCT4 were over-expressed in cancer tissues compared with that in normal tissues. MiRNA-145, SOX2, and OCT4 were expressed at similar levels in two cancer sites of a given DPEEOC or metastatic DEEOC sample. Besides, metastatic DEEOC sections expressed a higher level of SOX2 and OCT4 compared to the corresponding DPEEOC tissues. Together, these results support the clonality of DPEEOCs. Moreover, SOX2 and OCT4 may have some implication in DPEEOC and metastatic DEEOC diagnosis.
双原发性子宫内膜样子宫内膜癌和卵巢癌（DPEEOC）是最常见的多发性妇科癌症。近年来，基因序列比较分析有力地支持了以下观点：散发性双子宫内膜样子宫内膜癌和卵巢癌（DEEOC）在原发性和转移性肿瘤中均存在克隆相关性。为了找到更多支持DPEEOC克隆性的证据，我们对癌症干细胞（CSC）进行了研究。SOX2和OCT4是CSC中的两个常见因子。微小RNA（miRNA）-145是一种小的非编码RNA，对CSC中的基因表达和肿瘤发生具有调节作用。本研究的目的是评估SOX2、OCT4和miRNA-145在DPEEOC肿瘤发生中的作用。在我们的研究中，选取了20例DPEEOC患者。还纳入了转移性DEEOC以及正常子宫内膜和卵巢组织。通过实时定量PCR检测miRNA-145的表达。采用免疫组织化学染色法检测OCT4和SOX2的表达。结果显示，与相应正常组织相比，DPEEOC子宫内膜组织中miRNA-145表达较低，而DPEEOC卵巢组织中miRNA-145表达较高。与正常组织相比，癌症组织中SOX2和OCT4均过度表达。在给定的DPEEOC或转移性DEEOC样本的两个癌灶中，miRNA-145、SOX2和OCT4的表达水平相似。此外，与相应的DPEEOC组织相比，转移性DEEOC切片中SOX2和OCT4的表达水平更高。总之，这些结果支持DPEEOC的克隆性。此外，SOX2和OCT4可能在DPEEOC和转移性DEEOC诊断中具有一定意义。
