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

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

Mingjie Zhang  1   2 , Hui Li  1   2 , Yuefeng Han  1   2 , Mengjun Wang  1   2 , Junjie Zhang  1   2 , Shiyin Ma  1   2
Affiliations

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

Mingjie Zhang et al. Medicine (Baltimore). .

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.

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Conflict of interest statement

The authors have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Immunostaining of SOX4, or ZEB1 or Slug and their related marker proteins E-cadherin, N-cadherin, β-catenin in LSCC. A, Positive staining of SOX4 in LSCC (100 magnification); scale bar,100 μm. B, Positive staining of ZEB1 in LSCC (100 magnification). C, Positive staining of Slug in LSCC (100 magnification). D, Positive staining of Twist in LSCC (100 magnification). E, Positive staining of E-cadherin in the LSCC (100 magnification). F, Positive staining of N-cadherin in LSCC (100 magnification). G, Positive staining of β-catenin in LSCC (100 magnification). LSCC = laryngeal squamous cell carcinoma.
Figure 1 (Continued)
Figure 1 (Continued)
Immunostaining of SOX4, or ZEB1 or Slug and their related marker proteins E-cadherin, N-cadherin, β-catenin in LSCC. A, Positive staining of SOX4 in LSCC (100 magnification); scale bar,100 μm. B, Positive staining of ZEB1 in LSCC (100 magnification). C, Positive staining of Slug in LSCC (100 magnification). D, Positive staining of Twist in LSCC (100 magnification). E, Positive staining of E-cadherin in the LSCC (100 magnification). F, Positive staining of N-cadherin in LSCC (100 magnification). G, Positive staining of β-catenin in LSCC (100 magnification). LSCC = laryngeal squamous cell carcinoma.
Figure 2
Figure 2
Kaplan–Meier analysis of the survival rate of patients with LSCC. A, Overall survival of all patients in relation to SOX4 expression (Log-rank = 16.671, P < .001). B, Overall survival of all patients in relation to ZEB1 expression (Log-rank = 7.478, P < .05).  C, Overall survival of all patients in relation to Slug expression (Log-rank = 2.766, P = .096). D, Overall survival of all patients in relation to Twist expression (Log-rank = 1.485, P = .223). LSCC = laryngeal squamous cell carcinoma.
Figure 3
Figure 3
Kaplan–Meier analysis of the survival rate of patients with LSCC. A, Overall survival of all patients in relation to the combined expression of SOX4 and Slug (log-rank = 10.979, P < .05). B, Overall survival of all patients in relation to the combined expression of SOX4 and ZEB1 (log-rank = 15.532, P < .001).  C, Overall survival of all patients in relation to the combined expression of SOX4 and Twist (log-rank = 7.624, P < .01). LSCC = laryngeal squamous cell carcinoma.
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References

    1. Agra IM, Ferlito A, Takes RP, et al. . Diagnosis and treatment of recurrent laryngeal cancer following initial nonsurgical therapy. Head Neck 2012;34:727–35. - PubMed
    1. Steuer CE, El-Deiry M, Parks JR, et al. . An update on larynx cancer. CA Cancer J Clin 2017;67:31–50. - PubMed
    1. Ferlito A, Haigentz M, Jr, Bradley PJ, et al. . Causes of death of patients with laryngeal cancer. Eur Arch Otorhinolaryngol 2014;271:425–34. - PubMed
    1. Lefebvre V, Dumitriu B, Penzo-Méndez A, et al. . Control of cell fate and differentiation by Sry-related high-mobility-group box (Sox) transcription factors. Int J Biochem Cell Biol 2007;39:2195–214. - PMC - PubMed
    1. Stros M, Launholt D, Grasser KD. The HMG-box: a versatile protein domain occurring in a wide variety of DNA-binding proteins. Cell Mol Life Sci 2007;64:2590–606. - PubMed

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