Investigating the Link between STAT4 Genetic Variants, STAT4 Protein Concentrations, and Laryngeal Squamous Cell Carcinoma - A Comprehensive Analysis of Clinical Manifestations

Sep 21, 2026

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Inflammatory STAT4 signaling and its protein effects may influence cancer development, but their role in laryngeal squamous cell carcinoma (LSCC) clinical features remains insufficiently characterized. This study assessed four STAT4 single nucleotide variants and serum STAT4 levels to test associations with LSCC risk and clinical manifestations. Genotyping used real-time PCR in 632 men, and STAT4 protein was quantified by ELISA. Results indicate specific alleles correlate with LSCC occurrence, stage, differentiation, and metastasis status.

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Abstract

Keywords

1. Introduction

Epidemiology of laryngeal squamous cell carcinoma

Pathogenesis and clinical presentation

Article Investigating the Link between STAT4 Genetic Variants, STAT4 Protein Concentrations, and Laryngeal Squamous Cell Carcinoma: A Comprehensive Analysis of Clinical Manifestations Enrika Pileckaite 1, Alvita Vilkeviciute 1,*, Loresa Kriauciuniene 1, Vykintas Liutkevicius 2 and Rasa Liutkeviciene 1 Citation: Pileckaite, E.; Vilkeviciute, A.; Kriauciuniene, L.; Liutkevicius, V.; Liutkeviciene, R. Investigating the Link between STAT4 Genetic Variants, STAT4 Protein Concentrations, and Laryngeal Squamous Cell Carcinoma: A Comprehensive Analysis of Clinical Manifestations. Int. J. Mol. Sci. 2024, 25, 10180. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms251810180 Academic Editors: Marko Tarle and Ivica Lukši´c Received: 9 August 2024 Revised: 18 September 2024 Accepted: 20 September 2024 Published: 22 September 2024 Copyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Neuroscience Institute, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania; [enrika.pileckaite@lsmu.lt](enrika.pileckaite@lsmu.lt) (E.P.); [loresa.kriauciuniene@lsmu.lt](loresa.kriauciuniene@lsmu.lt) (L.K.); [rasa.liutkeviciene@lsmu.lt](rasa.liutkeviciene@lsmu.lt) (R.L.) 2 Department of Otorhinolaryngology, Lithuanian University of Health Sciences, LT-44307 Kaunas, Lithuania; [vykintas.liutkevicius@lsmu.lt](vykintas.liutkevicius@lsmu.lt) * Correspondence: [alvita.vilkeviciute@lsmu.lt](alvita.vilkeviciute@lsmu.lt) Abstract: According to recent research, inflammatory STAT4 and its protein impact may be important factors in developing cancerous diseases. Still unanalyzed is this effect in patients with laryngeal squamous cell carcinoma (LSCC) . In the present study, we evaluated four single nucleotide variants (SNVs) of STAT4 (rs10181656, rs7574865, rs7601754, and rs10168266) and STAT4 serum levels to determine their link between LSCC development and its clinical manifestations. A total of 632 men (324 LSCC patients and 338 healthy individuals) were involved in this study. The genotyping was carried out using real-time PCR. Additionally, we measured 80 study subjects’(40 LSCC patients and 40 control subjects) STAT4 protein concentrations using an enzyme-linked immunosorbent assay (ELISA) . In our study, the T allele of STAT4 rs7574865 significantly increases the likelihood of LSCC occurrence by 1.4-fold. Additionally, this SNV is associated with higher odds of early-stage disease, T1 size LSCC development, absence of metastasis to neck lymph nodes, and well-differentiated carcinoma. The G allele of rs10181656 is significantly associated with various clinical characteristics of LSCC, increasing the odds of early-and advanced-stage disease by 2.8-fold and 1.9-fold, respectively. Additionally, this allele is linked to an increased likelihood of developing tumors of different sizesand non-metastasized LSCC, as well as poorly differentiated carcinoma, highlighting its potential impact on the development and features of LSCC. Conclusion: The analysis of the STAT4 rs7574865 SNV revealed that the G allele is linked to a more favorable prognosis in LSCC. Additionally, it is hypothesized that the G allele of rs10181656 may be associated with the occurrence of LSCC but may not serve as a sensitive prognostic biomarker for distinguishing between disease stages, cell differentiation, or tumor size. Keywords: laryngeal squamous cell carcinoma; STAT4; single nucleotide variants; rs10181656; rs7574865; rs7601754; and rs10168266 1. Introduction One of the most frequently diagnosed malignant tumors of the head and neck region is laryngeal cancer, which accounts for more than 98% of all cancer

FAQs

What was the main goal of evaluating STAT4 in this study?

To determine whether STAT4 genetic variants and serum STAT4 protein concentrations are linked to LSCC development and its clinical manifestations.

Which methods were used for genotyping and measuring STAT4 protein levels?

Genotyping was performed using real-time PCR, and STAT4 protein concentrations were measured using ELISA.

How did STAT4 rs7574865 relate to LSCC occurrence and disease features?

The T allele of rs7574865 increased the likelihood of LSCC occurrence and was associated with early-stage disease, specific tumor size characteristics, absence of neck lymph node metastasis, and well-differentiated carcinoma.

Sep 21, 2026

Uploaded by Miles