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

Medicine (Baltimore). 2021 Mar 26;100(12):e25028. doi: 10.1097/MD.0000000000025028.

Abstract

Background and aim: 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, lymphatic invasion, and pathological tumor node metastasis (TNM) of a tumor. The expression rates of ZEB1, Twist, E-cadherin, N-cadherin, and β-catenin in LSCC correlated with lymphatic invasion and pathological tumor node metastasis. The expression of SOX4, combined expression of SOX4 and ZEB1, and lymphatic invasion 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.

MeSH terms

  • Antigens, CD / genetics
  • Biomarkers, Tumor / genetics*
  • Cadherins / genetics
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology*
  • Epithelial-Mesenchymal Transition / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / pathology*
  • Lymphatic Metastasis
  • Male
  • Nuclear Proteins / genetics
  • Prognosis
  • SOXC Transcription Factors / genetics*
  • Snail Family Transcription Factors / genetics
  • Twist-Related Protein 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / genetics
  • beta Catenin / genetics

Substances

  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • CDH2 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Nuclear Proteins
  • SNAI1 protein, human
  • SOX4 protein, human
  • SOXC Transcription Factors
  • Snail Family Transcription Factors
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • beta Catenin