ABSTRACT

Endometrial carcinoma (EC) remains one of the most prevalent forms of cancer to impact the female reproductive system, yet the mechanisms governing its development and progression are incompletely understood. We, therefore, sought to assess the relevance of SOX8 to EC progression and patient prognosis.

Array comparative genomic hybridization (aCGH) was performed using samples from 50 patients with EC. Samples were separated based upon whether patients were positive for lymph node metastasis (LN+ and LN−, respectively). Based on our initial results, the SOX8 gene was selected for further analysis. Immunohistochemical staining of 630 endometrial tissue samples was conducted to understand how SOX8 expression relates to specific EC clinicopathological characteristics. In addition, we explored the impact of SOX8 expression on the growth, invasion, and migration of EC cells through knockdown and overexpression experiments.

In our initial aCGH analysis, SOX family proteins and the Wnt and Notch signaling pathways were significantly associated with EC LN metastasis. SOX8 expression was markedly increased in EC tumor samples relative to normal endometrial tissue (P= .003), and higher SOX8 expression was linked to a high tumor histological grade (P= .032), LN metastasis (P= .027), and shorter patient overall survival (P= .031). When SOX8 was knocked down, this further impaired the proliferative, invasive, and migratory activity of EC cells, whereas overexpressing this gene had the opposite effect.

SOX8 may function in an oncogenic manner to drive EC development and progression, and higher SOX8 expression is associated with a poor EC patient prognosis.

摘要

子宫内膜癌 (EC) 仍然是影响女性生殖系统的最普遍的癌症形式之一，但控制其发展和进展的机制尚不完全清楚。因此，我们试图评估 SOX8 与 EC 进展和患者预后的相关性。

使用来自 50 名 EC 患者的样本进行阵列比较基因组杂交 (aCGH)。根据患者是否对淋巴结转移呈阳性（分别为 LN+ 和 LN-）来分离样品。根据我们的初步结果，选择了 SOX8 基因进行进一步分析。对 630 个子宫内膜组织样本进行免疫组织化学染色，以了解 SOX8 表达如何与特定的 EC 临床病理特征相关。此外，我们通过敲低和过表达实验探讨了 SOX8 表达对 EC 细胞生长、侵袭和迁移的影响。

在我们最初的 aCGH 分析中，SOX 家族蛋白以及 Wnt 和 Notch 信号通路与 EC LN 转移显着相关。与正常子宫内膜组织相比，EC 肿瘤样本中 SOX8 的表达显着增加 ( P = .003)，并且较高的 SOX8 表达与高肿瘤组织学分级 ( P = .032)、LN 转移 ( P = .027) 和更短的患者总生存期 ( P = .031)。当 SOX8 被敲低时，这进一步削弱了 EC 细胞的增殖、侵袭和迁移活性，而过表达该基因会产生相反的效果。

SOX8 可能以致癌方式起作用以驱动 EC 的发展和进展，并且较高的 SOX8 表达与 EC 患者的不良预后相关。