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

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 sizes and 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.

The survival rate of laryngeal squamous cell carcinoma: impact of IL1RAP rs4624606, IL1RL1 rs1041973, IL-6 rs1800795, BLK rs13277113, and TIMP3 rs9621532 single nucleotide polymorphisms.

PURPOSE: Results of laryngeal squamous cell carcinoma (LSCC) treatment and the 5 year survival rate of these patients remain poor. To purify therapeutic targets, investigation of new specific and prognostic blood-based markers for LSCC development is essential. METHODS: In the present study, we evaluated five single nucleotide polymorphisms (SNPs): IL1RAP rs4624606, IL1RL1 rs1041973, IL-6 rs1800795, BLK rs13277113, and TIMP3 rs9621532, and determined their associations with the patients' 5 year survival rate. Also, we performed a detailed statistical analysis of different LSCC patients' characteristics impact on their survival rate. RESULTS: Three hundred fifty-three LSCC patients and 538 control subjects were included in this study. The multivariable Cox regression analysis revealed a significant association between patients' survival rate and distribution of IL1RAP rs4624606 variants: patients carrying AT genotype at IL1RAP rs4624606 had a lower risk of death (p = 0.044). Also, it was revealed that tumor size (T) (p = 0.000), tumor differentiation grade (G) (p = 0.015), and IL1RAP rs4624606 genotype (p = 0.044) were effective variables in multivariable Cox regression analysis prognosing survival of LSCC patients. The specific-LSCC 5 year survival rate was 77%. CONCLUSIONS: In summary, our findings indicate that the genotypic distribution of IL1RAP rs4624606 influences the 5 year survival rate of LSCC patients. The results of the present study facilitate a more complete understanding of LSCC at the biological level, thus providing the base for the identification of new specific and prognostic blood-based markers for LSCC development.

The Role of ApoE Serum Levels and ApoE Gene Polymorphisms in Patients with Laryngeal Squamous Cell Carcinoma.

Recent studies have revealed that the inflammatory ApoE effect may play a significant role in various cancer development. However, this effect has still not been analyzed in patients with laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated two single nucleotide polymorphisms (SNPs) of ApoE (rs7412 and rs429358) and determined their associations with LSCC development and the LSCC patients' five-year survival rate. Additionally, we analyzed serum ApoE levels using an enzyme-linked immunosorbent assay. A total of 602 subjects (291 histologically verified LSCC patients and 311 healthy controls) were involved in this study. The genotyping was carried out using the real-time PCR. We revealed that ApoE ε3/ε3 was associated with a 1.7-fold higher probability of developing LSCC (p = 0.001), with 1.7-fold increased odds of developing LSCC without metastasis to the lymph nodes (p = 0.002) and with a 2.0-fold increased odds of developing well-differentiated LSCC (p = 0.008), as well as 1.6-fold increased odds of developing poorly differentiated LSCC development (p = 0.012). The ApoE ε2/ε4 and ε3/ε4 genotypes were associated with a 2.9-fold and 1.5-fold decrease in the likelihood of developing LSCC (p = 0.042; p = 0.037, respectively). ApoE ε3/ε4 was found associated with a 2.4-fold decreased likelihood of developing well-differentiated LSCC (p = 0.013). Conclusion: ApoE ε2/ε4 and ε3/ε4 were found to play a protective role in LSCC development, while ApoE ε3/ε3 may have a risk position in LSCC development.

Factors Affecting the Lifetime of Third-Generation Voice Prosthesis After Total Laryngectomy.

PURPOSE: The study aimed to evaluate the impact of different variables on the longevity of Voice Prosthesis (VP) in patients after total laryngectomy. PATIENTS AND METHODS: This retrospective cohort study is based on data about a continuous series of 328 third-generation VP, which were implanted between 2016 and 2020. Data about the VP users' age, sex, place of residence, laryngeal tumor stage, neck irradiation, VP size, and the use of Heat and Moisture Exchanger (HME) were obtained and analyzed. The effect of these variables on VP lifetime was determined. RESULTS: The median lifetime of VPs in patients 65 years old and above was 182 days (95% CI 168-196), versus 146 days (95% CI 130-162) (P = 0.033) in patients younger than 65. Neck irradiation was associated with a longer VP median lifetime of 161 days (95% CI 142-180) compared to 126 days (95% CI 100-152) with no prior neck irradiation (P = 0.046). HME usage was associated with significantly increased longevity of VPs: 182 days (95% CI 156-208) with HME and 149 days (95% CI 132-166) without HME usage (P = 0.039). CONCLUSION: The results of the present study suggest that neck irradiation, and routine use of use of HME are positively associated with the longevity of VPs.

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

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.

Investigation of Relationship Between Auditory-Perceptual Methods and Self-reported Speech Handicap Index in the Assessment of Substitution Voicing.

OBJECTIVE: To assess correlations between auditory-perceptual and self-reported speech evaluation methods for substitution voicing (SV) and to investigate the robustness of these methods in a clinical setting. METHODS: Fifty-nine male patients who underwent laryngeal oncosurgery and 62 healthy male controls were included in this prospective study. Lithuanian versions of the Speech Handicap Index (SHI-LT) and Impression of voice quality (I), Impression of intelligibility (I), Unintended additive Noise (N), Fluency (F), and Quality of Voicing (Vo) scale (IINFVo-LT) were used to assess and compare self-reported and auditory-perceptual evaluations of SV. Speech samples were rated by a panel of experienced raters. RESULTS: The IINFVo-LT revealed good inter-rater reliability (ICC = 0.825) and intrarater reliability over time (ICC = 0.976) when assessing SV. Statistically significant differences (P < 0.05) of the mean scores of IINFVo-LT among the cordectomy, partial laryngectomy (22.52 [SD 9.98]), tracheoesophageal prosthesis (16.92 [SD 10.71]), and control (48.01 [SD 2.88]) groups confirmed the usefulness of IINFVo-LT for SV rating. A moderate negative correlation (r = -0.61; P < 0.001) demonstrated good concurrent validity between the IINFVo-LT and the SHI-LT total scores. A statistically significant, strong, negative correlation (r = -0.74) was obtained between the IINFVo-LT and SHI-LT speech handicap grade (P < 0.001), demonstrating good concurrent validity. CONCLUSION: The combination of IINFVo-LT and SHI-LT represents a potentially valuable and robust tool for evaluating SV and is helpful for assessing the degree of speech abnormality after laryngeal oncosurgery and its impact on patients' quality of life.

Associations of Polymorphisms Localized in the 3'UTR Regions of the KRAS, NRAS, MAPK1 Genes with Laryngeal Squamous Cell Carcinoma.

BACKGROUND: Genetic variations, localized in the 3' untranslated region (UTR) in mitogen-activated protein kinase (MAPK) pathway-related genes, may alter the transcription and impact the pathogenesis of laryngeal squamous cell carcinoma (LSCC). The present study investigated the associations of single-nucleotide polymorphisms (SNP), localized in the 3'UTR) of the KRAS, NRAS, and MAPK1 genes with LSCC risk and clinicopathological features. METHODS: Genomic DNA and clinical data were collected from 327 adult men with LSCC. The control group was formed from 333 healthy men. Genotyping of the SNPs was performed using TaqMan SNP genotyping assays. Five KRAS, NRAS, and MAPK1 polymorphisms were analyzed. All studied genotypes were in Hardy-Weinberg equilibrium and had the same allele distribution as the 1000 Genomes project Phase 3 dataset for the European population. RESULTS: Significant associations of the studied SNPs with reduced LSCC risk were observed between NRAS rs14804 major genotype CC. Significant associations of the studied SNPs with clinicopathologic variables were also observed between NRAS rs14804 minor T allele and advanced tumor stage and positive lymph node status. SNP of MAPK1 rs9340 was associated with distant metastasis. Moreover, haplotype analysis of two KRAS SNPs rs712 and rs7973450 revealed that TG haplotype was associated with positive lymph node status in LSCC patients. CONCLUSIONS: According to the present study, 3'UTR SNP in the NRAS and MAPK1 genes may contribute to the identifications of patients at higher risk of LSCC lymph node and distant metastasis development.

The Role of IL-9 Polymorphisms and Serum IL-9 Levels in Carcinogenesis and Survival Rate for Laryngeal Squamous Cell Carcinoma.

Recent studies have described the dichotomous function of IL-9 in various cancer diseases. However, its function has still not been analysed in laryngeal squamous cell carcinoma (LSCC). In the present study, we evaluated five single nucleotide polymorphisms (SNPs) of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) and determined their associations with the patients' five-year survival rate. Additionally, we analysed serum IL-9 levels using an enzyme-linked immunosorbent assay. Three hundred LSCC patients and 533 control subjects were included in this study. A significant association between the patients' survival rate and distribution of IL-9 rs1859430 variants was revealed: patients carrying AA genotype had a higher risk of dying (p = 0.005). Haplotypes A-G-C-G-G of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) were associated with 47% lower odds of LSCC occurrence (p = 0.035). Serum IL-9 levels were found detectable in three control group subjects (8.99 ± 12.03 pg/mL). In summary, these findings indicate that the genotypic distribution of IL-9 rs1859430 negatively influences the five-year survival rate of LSCC patients. The haplotypes A-G-C-G-G of IL-9 (rs1859430, rs2069870, rs11741137, rs2069885, and rs2069884) are associated with the lower odds of LSCC development.

Impact of IL-10 Promoter Polymorphisms and IL-10 Serum Levels on Advanced Laryngeal Squamous Cell Carcinoma and Survival Rate.

BACKGROUND/AIM: Prognosis of advanced stages of laryngeal squamous cell carcinoma (LSCC) remains poor. To clarify therapeutic targets and improve survival rate, identification of new specific and prognostic biomarkers of LSCC is required. The study aimed to evaluate the impact of IL-10:rs1800871, rs1800872, rs1800896 single nucleotide polymorphisms (SNPs), and IL-10 serum levels on LSCC development and determine associations of selected SNPs with patient survival rate. PATIENTS AND METHODS: A total of 300 LSCC patients and 533 controls were included in the study. Genotyping was carried out using RT-PCR; IL-10 serum levels were analyzed by ELISA. RESULTS: Significant associations were identified between IL-10 rs1800871 variants and advanced stage of LSCC patient group in the codominant, recessive and additive models (OR=0.473, p=0.027; OR=0.510, p=0.040; and OR=0.733; p=0.037). Significant variants of IL-10 rs1800872 were determined in the codominant, recessive and additive models (OR=0.473, p=0.027; OR=0.510, p=0.040; and OR=0.733, p=0.037). The distribution of IL-10 SNPs genotypes did not impact LSCC patient survival rate (respectively, p=0.952; p=0.952; p=0.991). CONCLUSION: IL-10:rs1800871 and rs1800872 SNPs are associated with advanced stage of LSCC. The genotypic distribution of IL-10 SNPs does not influence the survival rate of LSCC patients.

Cross-cultural adaptation and validation of Lithuanian-NOSE scale.

PURPOSE: To evaluate validity and reliability of Lithuanian version of Nasal Obstruction Symptom Evaluation Scale (L-NOSE), designed for the assessment of nasal obstruction. METHODS: Cross-cultural adaptation of L-NOSE was accomplished according to generally accepted methodology. L- NOSE was tested for its reliability, validity, and responsiveness in the group of 50 septoplasty patients and 100 healthy volunteers' controls. RESULTS: L- NOSE showed good internal consistency (Cronbach's alpha coefficient 0.796 for test, 0.791 for retest, 0.792 for post-operative group, and 0.817 for control group) scores and high test-retest reliability (r = 0.94, p < 0.01) scores. In patients' group, positive moderate correlations between L-NOSE scores and Sino-nasal Outcome Test-22 logically similar domain scores were found, thus indicating good convergent construct validity. L-NOSE scores for control subjects were generally lower than for patients with nasal obstruction (p < 0.001), thereby indicating good discriminant validity of questionnaire. The exploratory factor analysis confirmed one-factor structure of questionnaire. The component matrix of L-NOSE ranged from 0.667 to 0.781 (KMO = 0.754, p < 0.0001). The mean L-NOSE score improved from 58.4 ± 18.2 points to 11.1 ± 9.5 points after septoplasty (p < 0.0001), indicating good responsiveness of questionnaire. CONCLUSION: The L-NOSE questionnaire is a valid instrument with satisfactory reliability, validity, and responsiveness.

Tendencies of FGFR2 rs2981582 polymorphism in patients with oral cancer.

OBJECTIVE: Fibroblast growth factor receptor 2 (FGFR2) is a member of the FGFR family of tyrosine kinase receptors, which via cell growth, invasiveness, motility and angiogenesis contributes to the process of tumorogenesis. A huge interest today is focused on FGFR2 gene polymorphism as it may have a significant impact on the development of various benign and malignant tumors. A case-control study was designed to help determine if FGFR2 gene polymorphism rs2981582 is associated with oral cancer in Lithuanian subjects. METHODS: The study included 35 patients with a diagnosis of oral cancer and 100 healthy subjects as a reference group. DNA samples were extracted from peripheral venous blood. Genotyping of FGFR2 rs2981582 was performed using the real-time polymerase chain reaction method. Statistical analysis was performed using "IBM SPSS Statistics 20.0". RESULTS: It was determined that FGFR2 gene rs2981582 polymorphism has no effect on a development of oral cancer. The analysis of FGFR2 gene polymorphisms did not reveal any differences in the distribution of GG, GA, and AA genotypes between the oral cancer group, and the control group (42.9%, 48.6%, and 8.6% vs. 46%, 37% and 17%, respectively). CONCLUSION: Results of present study showed no association between FGFR2 gene polymorphisms rs2981582 and oral cancer. However, a further study with a larger sample sizes is advisable.

Association of Leukocyte Telomere Length and Genes Involved in its Regulation With Oral Carcinoma.

BACKGROUND/AIM: This study aimed to determine the relationship between the relative leukocyte telomere length (RLTL) and gene polymorphisms involved in its regulation with the occurrence of oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: Patients with OSCC and healthy subjects were examined. Genotyping and RLTL measurement were carried out using rPCR. RESULTS: The OSCC group had longer telomeres than controls (p=0.001). Minor allele T at TERF1rs1545827 may increase RLTL shortening (p=0.047). TNKS2rs10509639 A/G and A/G+G/G genotypes were associated with a 2.6-fold increased odd (p=0.012) and a 2.4-fold increased odd (p=0.019) of RLTL elongation compared to A/A genotype. The A/G genotype was associated with a 2.6-fold increased odd (p=0.011) compared to the A/A+G/G genotypes. Each G allele was associated with a 2.1-fold increased odd of longer RLTL (p=0.036). CONCLUSION: Longer telomeres were found in patients with OSCC than in controls. The TERF1 rs1545827 and the TNKS2 rs10509639 polymorphisms were associated with an increase in RLTL.

Association of Relative Leucocyte Telomere Length and Gene Single Nucleotide Polymorphisms (TERT, TRF1, TNKS2) in Laryngeal Squamous Cell Carcinoma.

BACKGROUND/AIM: The study aimed to evaluate associations of relative leukocyte telomere length (LTL) and polymorphisms of telomere length-associated genes TERT (rs2736098), TERT-CLPTM1L (rs401681), TRF1 (rs1545827, rs10107605) and TNKS2 (rs10509637, rs10509639) in patients with laryngeal squamous cell carcinoma (LSCC). MATERIALS AND METHODS: The study consisted of 300 patients with LSCC and 369 healthy control subjects. Genotyping and relative LTL measuring were carried out using qPCR. RESULTS: Relative LTL was statistically significantly shorter in the G3 (tumor differentiation grade) subgroup of patients with LSCC compared to the G1 and G2 subgroups. Significant differences were found in genotype distributions of TERT rs401681 and TNKS2 rs10509639 between the study groups. TERT rs401681 C/T and T/T genotypes were associated with approximately 30% decreased odds of LSCC development. CONCLUSION: LTL was shorter in the G3 subgroup compared to the G2 and G1 subgroups of LSCC patients. TERT rs401681 and its C/T and T/T genotypes were associated with decreased odds of overall LSCC development.

Association Between MMP8 Gene Polymorphisms and Laryngeal Squamous Cell Carcinoma.

BACKGROUND/AIM: Matrix metalloproteinases (MMPs) are a family of proteins which are involved in breakdown of the extracellular matrix in embryonic development, tissue remodeling and in some diseases. MMP8 has both cancer-promoting and anticancer properties. However, the contribution of MMP8 to laryngeal squamous cell carcinoma (LSCC) has not been elucidated. In this study we aimed to test the contribution of two MMP8 polymorphisms, located in the gene promoter region, to the development of LSCC. MATERIALS AND METHODS: This case-control study involved 569 DNA samples which were genotyped for two single nucleotide polymorphisms using real-time polymerase chain reaction method. Statistical analysis was performed with SPSS Statistics 20 software. RESULTS: Regression analysis adjusted by age showed that for MMP8 rs11225395 each minor A allele copy significantly reduced the odds for LSCC development (odds ratio=0.49, 95% confidence intervaI=0.04-2.19, p=0.048). MMP8 rs11225395 AA genotype was associated with smaller laryngeal tumour size (p=0.023). Smoking habit also correlated with laryngeal tumor size. CONCLUSION: MMP8 rs11225395 and smoking habits have a prominent interface with LSCC tumour size.

Associations of IL6 rs1800795, BLK rs13277113, TIMP3 rs9621532, IL1RL1 rs1041973 and IL1RAP rs4624606 single gene polymorphisms with laryngeal squamous cell carcinoma.

OBJECTIVE: Survival rate of laryngeal squamous cell carcinoma (LSCC) patients is not improving. To understand more complete biology of LSCC, studies focused on identification of new specific and prognostic markers are performed. The aim of current study was to evaluate the impact of five different single nucleotide polymorphisms (SNP) (IL6 rs1800795, BLK rs13277113, TIMP3 rs9621532, IL1RL1 rs1041973 and IL1RAP rs4624606) on LSCC development. MATERIAL AND METHODS: A total of 891 subjects (353 histologically verified LSCC patients and 538 healthy controls) were involved in this study. The genotyping was carried out using the real-time-PCR. RESULTS: Statistical analysis revealed statistically significant associations between TIMP3 rs96215332 variants and LSCC in the codominant (OR = 0.600; 95% CI: 0.390-0.922; p = 0.020), overdominant (OR = 0.599; 95% CI: 0.390-0.922; p = 0.020) and additive (OR = 0.675; 95% CI: 0.459-0.991; p = 0.045) models. Also, significant variants of IL1RAP rs4624606 were determined in the codominant (OR = 1.372; 95% CI: 1.031-1.827; p = 0.030), overdominant (OR = 1.353; 95% CI: 1.018-1.798; p = 0.037) and additive (OR = 1.337; 95% CI: 1.038-1.724; p = 0.025) models. CONCLUSION: Results of the current study indicate significant associations between TIMP3 rs9621532 and IL1RAP rs4624606 gene polymorphisms and LSCC development.

Matrix Metalloproteinases (MMP-2,-3,-9) Gene Polymorphisms in Cases of Benign Vocal Fold Lesions and Laryngeal Carcinoma.

BACKGROUND/AIM: The matrix metalloproteinases (MMP) play an important role in the physiological and pathological remodeling of tissues including carcinogenesis. The study's aim was to assess the relations between MMP-2(-735C/T), MMP-2(-1306C/T), MMP-9(-1562C/T), and MMP-3(-11715A/6A) polymorphisms, and clinical/morphological manifestation of laryngeal squamous cell carcinoma (LSCC) and benign vocal fold lesions (BVFL). PATIENTS AND METHODS: Two hundred and seventeen patients with LSCC and BVFL and 458 controls were included in this study. The genotyping was performed using the real-time polymerase chain reaction method. RESULTS: The MMP-2(-1306C/T) C/T genotype was significantly rarer among the patients with moderate-poorly differentiated LSCC compared to the control group, however the MMP-3(-11715A/6A) 6A/6A genotype was significantly more frequent compared to controls. Smoking and 6A/6A genotype of MMP-3(-11715A/6A) polymorphism were associated with increased odds of LSCC risk. No associations between MMP genotypes and BVFL were found. CONCLUSION: Smoking and MMP-3 (-11715A/6A) 6A/6A genotype may cause a higher risk for developing LSCC.

Determination of SIRT1 rs12778366, FGFR2 rs2981582, STAT3 rs744166, and RAGE rs1800625 Single Gene Polymorphisms in Patients with Laryngeal Squamous Cell Carcinoma.

PURPOSE: To determine the frequency of the genotype of signal transducer and activator of transcription protein 3 (STAT3) rs744166, sirtuin (SIRT1) rs12778366, fibroblast growth factor (FGFR2) rs2981582, and advanced glycosylation end product-specific receptor (RAGE) rs1800625 gene polymorphisms in patients with laryngeal squamous cell carcinoma (LSCC). METHODS: A total of 944 subjects were evaluated, which includes 144 patients with LSCC and 800 healthy controls. The genotyping of STAT3 rs744166, SIRT1 rs12778366, FGFR2 rs2981582, and RAGE rs1800625 was carried out using the RT-PCR. RESULTS: The analysis of STAT3 rs744166, SIRT1 rs12778366, and FGFR2 rs2981582 gene polymorphisms did not reveal any differences in genotype distribution between the patients with LSCC and the control subjects. However, statistical analysis revealed that genotypes (AA, AG, and GG) of rs1800625 in RAGE gene were distributed statistically significantly differently between patients and controls (61.1%, 30.6%, and 23.6% vs. 72.5%, 25.8%, and 1.8%, respectively; p < 0.001). Additionally, statistical significance was observed in allele distribution between these two groups, i.e., allele G at rs1800625 was more frequently observed in the patient group than in controls (23.6% vs. 14.6%; p < 0.001). CONCLUSION: RAGE rs1800625 gene polymorphism may play a significant role in laryngeal squamous cell carcinoma development.

Glottal function index questionnaire for screening of pediatric dysphonia.

OBJECTIVE: to assess the diagnostic value of Lithuanian version of Glottal Function Index (GFI-LT) questionnaire in pediatric dysphonia screening. METHODS: The GFI-LT was completed by 82 children (7-16 years old): 41 patients with voice disorders (patients group) and 41 healthy subjects (control group). Auditory-perceptual evaluation of voice was performed using the Grade Roughness Breathiness (GRB) protocol. Acoustic voice analysis was accomplished for F0, SDF0, jitter, shimmer and NNE using Dr. Speech, Tiger Elemetrics software. To evaluate the diagnostic accuracy differentiating normal and dysphonic voice, the receiver operating characteristic statistics were used. RESULTS: Perceptually dysphonia was revealed in all children of the patients group. Grade I (65.9%) was the most prevalent (p > 0.05). No dysphonia was detected in the control group. Acoustic voice analysis revealed statistically significantly (p < 0.001) deteriorated all acoustic voice parameters in patients' group comparing to control group. Statistically significant (p < 0.05) strong or moderate correlations were found between the GFI-LT, auditory-perceptual rating and all acoustic voice parameters of the patients group. The strongest correlations were observed between GFI-LT and G (r = 0.70), R (r = 0.69), jitter (r = 0.56) and SDF0 (r = 0.56). No statistically significant correlations between GFI-LT and children' age or gender were found (p > 0.05). The GFI-LT cut-off score of ≥3.0 was associated with excellent test accuracy (AUC = 0.961) distinguishing children with voice disorders from healthy controls, resulting in a balance between sensitivity and specificity (95.1% vs 85.4%). CONCLUSION: GFI-LT is considered to be a valid and reliable tool for self-assessment and screening of voice disorders in children.

Validation of the Lithuanian Version of the Speech Handicap Index.

OBJECTIVE: The objective is to study the cultural adaptation and validation of the Speech Handicap Index (SHI) questionnaire to the Lithuanian language. METHODS: Cultural adaptation and validation of the translated Lithuanian version of the SHI (SHI-LT) was performed as described by the Scientific Advisory Committee of the Medical Outcomes Trust. The SHI-LT was completed by 46 patients after total laryngectomy and by 60 healthy subjects of the control group. Validity and reliability of the SHI-LT were evaluated. RESULTS: The SHI-LT showed a statistically significant high internal consistency and test-retest reliability (Cronbach's α = 0.96-0.98). Good validity of SHI-LT was reflected by statistically significant (P < 0.001) difference between the mean scores of the patients and control groups (74.7 ± 26.9 and 5.5 ± 6.5, respectively). No age or gender dependence of SHI-LT was found (P > 0.05). Receiver operating characteristic test indicated that SHI-LT scores exceeding 17.0 points (cutoff value) distinguish patients from healthy controls, with a sensitivity of 97.8% and specificity of 95.0%. CONCLUSION: SHI-LT is considered to be a valid and reliable speech assessment tool for Lithuanian-speaking patients after laryngectomy.

Characteristics of Expression of Matrix Metalloproteinases (MMP-2 and MMP-9) in Glottic Squamous Cell Carcinoma and Benign Vocal Fold Lesions.

OBJECTIVES: The aim of this study was to investigate expression profile of matrix metalloproteinases (MMP-2 and MMP-9) in glottic squamous cell carcinoma (SCC) and benign vocal fold lesions (BVFLs) and to correlate it with clinical and pathological features. METHODS: The immunohistochemical expression of MMP-2 and MMP-9 was investigated in specimens taken from 217 patients group, including vocal fold polyps (n=39), recurrent respiratory papillomatosis (n=30), laryngeal keratosis (n=36), glottic SCC (n=112), and the normal tissue of vocal fold (n=12, control group). The expression of MMP-2 and MMP-9, both in epithelium and stroma cells, was graded on a semiquantitative scale, ranging from 0 (no expression) to 18 points (high expression). RESULTS: Expressions of both, MMP-2 and MMP-9 were significantly higher in the glottic SCC group comparing with BVFL group. Significant higher expression of parenchymal MMP-2 (P<0.001) and stromal MMP-9 (P=0.01) was revealed in the group of moderate/poorly differentiated glottic SCC comparing with well differentiated glottic SCC group. Expression of stroma MMP-2 was found to be correlated with nodal metastasis (P=0.030). Expressions of both, MMP-2 and MMP-9 were not correlated with clinical stage, tumor T value, smoking, alcohol use, age in the glottic SSC patients group. The MMP-2 stroma value of 11.2 points was determined as the optimum point (limiting value) for separating BVFL and glottic SCC patient groups. CONCLUSION: Our results suggest that expressions of both MMP-2 and MMP-9 are up-regulated already in the development of BVFL, the next determinant step is concerned with occurrence of malignization. Limiting value of stroma MMP-2 demonstrates prognostic importance of MMP-2 in glottic SCC carcinogenesis.