The oncogenic role of SOX8 in endometrial carcinoma

Cancer Biol Ther. 2020 Dec 1;21(12):1136-1144. doi: 10.1080/15384047.2020.1840318. Epub 2020 Nov 16.

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.

Keywords: Endometrial carcinoma; SOX8; lymph node metastasis; oncogene; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Disease Progression
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / pathology
  • Female
  • Humans
  • Oncogenes / genetics*
  • Prognosis
  • SOXE Transcription Factors / metabolism*

Substances

  • SOX8 protein, human
  • SOXE Transcription Factors

Grants and funding

This research work was supported by the National Natural Science Foundation of China (no. 81572568, 81972448, 81772790) and the Tianjin Science and Technology Plan Project(no. 20JCZDJC00330).