Association of SIRT1 single gene nucleotide polymorphisms and serum SIRT1 levels with laryngeal squamous cell carcinoma patient survival rate

Abstract

BACKGROUND: SIRT1 is a multifunctional protein, possibly essential in tumorigenesis pathways, which can act both as a tumor promoter and tumor suppressor depending on the oncogenes, specific to particular tumors. Pathogenesis of laryngeal cancer is multifactorial and the association of SIRT1 expression with the clinical characteristics and prognosis of LSCC has not been fully identified. OBJECTIVES: The study aimed to evaluate associations between single gene nucleotide polymorphisms (SNPs) of SIRT1 (rs3818292, rs3758391, and rs7895833), serum SIRT1 levels, and 5-year survival rate in patients with laryngeal squamous cell carcinoma (LSCC). METHODS: The study involved 302 patients with LSCC and 409 healthy control subjects. The genotyping of SNPs was performed using RT-PCR, and serum SIRT1 levels were determined by the ELISA method. RESULTS: Our study found significant differences in genotype distributions of SIRT1 rs3758391 polymorphisms between the study groups. SIRT1 rs3758391 T/T genotype was associated with the increased LSCC development odds (OR = 1.960 95% CI = 1.028–3.737; p= 0.041). Carriers of SIRT1 rs3758391 T/T genotype had statistically significantly increased odds of LSCC development into advanced stages under the codominant and recessive genetic models (OR = 2.387 95% CI = 1.091–5.222; p= 0.029 and OR = 2.287 95% CI = 1.070–4.888; p= 0.033, respectively). There were no statistically significant differences in serum SIRT1 levels between the LSCC and control groups. However, LSCC patients with SIRT1 rs3818292 AG genotype demonstrated a tendency to significantly lower SIRT1 serum levels than controls (p= 0.034). No statistically significant associations between SIRT1 (rs3818292, rs3758391, and rs7895833) SNPs and the 5-year survival rate of LSCC patients were found. CONCLUSION: The present study indicated a statistically significant association between the SIRT1 rs3758391 T/T genotype and increased LSCC development odds. LSCC patients with SIRT1 rs3818292 AG genotype showed a tendency to manifest with lower SIRT1 serum levels. No associations between SIRT1 SNPs and the 5-year survival rate of LSCC patients were detected.

Targeting histone deacetylases in head and neck squamous cell carcinoma: molecular mechanisms and therapeutic targets

“…It also hindered EMT in OSCC by suppressing Smad2/3 phosphorylation and Smad4 deacetylation [84]. Disruption of SIRT1-induced deacetylation of c-JUN by miR-135b-5p promoted migration and invasion in NPC cells [85]. The Kaplan-Meier survival analysis further demonstrated that patients with increased levels of SIRT1 experienced significantly prolonged overall survival, as indicated by Logrank p < 0.05 (Fig.…”

“…SIRT1 expression was found to be predominant in cases involving patients aged over 65 years, lymph node negative and early clinical stage cases for HNSCC [86], suggesting its potential as a valuable prognostic assessment tool. The single gene nucleotide polymorphisms (SNPs) in SIRT1 were linked to the survival rate of LSCC patients [85]. Notably, the SIRT1 rs3758391 T/T genotype demonstrated a significant association with an elevated likelihood of developing LSCC [85].…”

“…The single gene nucleotide polymorphisms (SNPs) in SIRT1 were linked to the survival rate of LSCC patients [85]. Notably, the SIRT1 rs3758391 T/T genotype demonstrated a significant association with an elevated likelihood of developing LSCC [85]. In OSCC, the overexpression of SIRT1 in Tca8113 cell lines led to cisplatin resistance, which could be reversed by BML-210, an inhibitor of class III HDACs [87].…”

Value of Serum Sirtuin-1 (SIRT1) Levels and SIRT1 Gene Variants in Periodontitis Patients

“…The following study also proved that the two SIRT1 rs1467568 and rs7895833 polymorphisms had an impact on the reduced risk of developing CRS1 in the Chinese population [ 26 ]. In the work of Vaiciulis et al, which focused on the study of laryngeals squamous cell carcinoma (LSCC) development probability, carriers of the SIRT1 rs3758391 T/T genotype had a statistically significant increased probability of developing advanced-stage LSCC, according to the codominant and recessive genetic model (OR = 2.387; 95% CI = 1.091–5.222; p = 0.029 and OR = 2.287; 95% CI = 1.070–4.888; p = 0.033, respectively) [ 27 ]. In contrast, in our study, we found no statistically significant differences in the development of periodontitis in the male population in our study.…”