Clinicopathological significance of SOX4 and epithelial-mesenchymal transition markers in patients with laryngeal squamous cell carcinoma

Auris Nasus Larynx. 2021 Dec;48(6):1167-1175. doi: 10.1016/j.anl.2021.04.013. Epub 2021 May 14.

Abstract

Objective: Sex-determining region-Y-related high-mobility-group box 4 (SOX4) is associated with the metastasis and prognosis of many cancer types. However, studies on the role of SOX4 in laryngeal squamous cell carcinoma (LSCC) are few, and hence the mechanism is unclear. Epithelial-mesenchymal transition (EMT) allows neoplastic cells to gain the plasticity and motility required for tumor progression and metastasis. This study aimed to analyze the relationship between SOX4 and EMT, and their relationship with clinicopathological factors and related prognosis.

Methods: Immunohistochemical staining was used to detect the positive expression of SOX4 protein, EMT-related transcription factor protein, and related marker protein in 127 LSCC tissue samples. At the same time, data on various parameters of clinical pathology and postoperative survival were collected.

Results: The positive expression rate of SOX4 and Slug in LSCC was related to pathological differentiation, Lymph node metastasis (LNM), and pathological TNM of a tumor. The expression rates of ZEB1, E-cadherin, N-cadherin, and β-catenin in LSCC correlated with LNM and pTNM. The expression of SOX4, combined expression of SOX4 and ZEB1, and LNM were independent prognostic factors for the total survival time of patients with LSCC.

Conclusions: In summary, SOX4 was vital in the LSCC EMT process, which might be mediated by transcription factor ZEB1. SOX4 and ZEB1 might serve as potential biomarkers of metastasis and prognosis, as well as promising therapeutic targets of LSCC.

Keywords: EMT; Laryngeal squamous cell carcinoma; SOX4; ZEB1.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Biomarkers, Tumor / metabolism*
  • Cadherins / metabolism
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / mortality
  • Laryngeal Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • SOXC Transcription Factors / metabolism*
  • Snail Family Transcription Factors / metabolism
  • Squamous Cell Carcinoma of Head and Neck / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / mortality
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism*

Substances

  • Biomarkers, Tumor
  • Cadherins
  • SNAI1 protein, human
  • SOX4 protein, human
  • SOXC Transcription Factors
  • Snail Family Transcription Factors
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1