BCL11A Promotes the Progression of Laryngeal Squamous Cell Carcinoma.

Background: We report functional and clinical data uncovering the significance of B-cell lymphoma/leukemia 11A (BCL11A) in laryngeal squamous cell carcinoma (LSCC). Methods: We examined BCL11A expression in a cohort of LSCC patients and evaluated the association between BCL11A expression and clinicopathological features. We investigated the consequences of overexpressing BCL11A in the LSCC cell line on proliferation, migration, invasion, cell cycle, chemosensitivity, and growth in vivo. We explored the relationship between BCL11A and MDM2 in LSCC and tumorigenesis pathways by using the Human Cancer PathwayFinder Array. Results: High levels of BCL11A were found in LSCC tissues and were more frequently associated with advanced lymphatic metastasis stages with poor prognoses. BCL11A overexpression enhanced LSCC proliferation in vitro and vivo. A positive correlation between MDM2 and BCL11A expression was identified. Conclusions: These data uncover important functions of BCL11A in LSCC and identify BCL11A as a prognostic biomarker and potential therapeutic target in LSCC.

Role of T helper 17 cytokines in the tumour immune inflammation response of patients with laryngeal squamous cell carcinoma.

Altered cytokine production can lead to immune dysfunction in patients with cancer. The present study investigated the expression of T helper (Th)17 cytokines in patients with laryngeal squamous cell carcinoma (LSCC) and their clinical significance in providing new therapeutic insights. The prevalence of Th17 cells and their receptors in patients with LSCC was studied using immunohistochemical analysis via tissue microarray technology. Flow cytometry was used to investigate the percentage of Th17 and Th1 cells in peripheral blood mononuclear cells. Furthermore, the proliferation of Th17 cells and Th17-associated cytokines, including interleukin (IL)17, IL23 and RAR-related orphan receptor γt, was analyzed by reverse transcription-quantitative polymerase chain reaction. The results revealed that the prevalence of Th17 cells in patients with LSCC was elevated in their primary tumors, as well as in peripheral blood, compared with that in healthy controls. It was further demonstrated that Th17 cells could be induced and expanded in the tumor microenvironment through cytokines produced by the tumor cells. In conclusion, Th17 cells have a substantial impact on the carcinogenesis of LSCCs, and could serve as a potential therapeutic target to modulate the anti-tumor response in these carcinomas.

Association of the microsatellite (GT)n repeat polymorphisms of the HO-1 gene promoter and corresponding serum levels with the risk of laryngeal squamous cell carcinoma.

CONCLUSION: Long (GT)n repeat polymorphisms in the heme oxygenase-1 (HO-1) gene promoter and decreased serum HO-1 levels are associated with a higher susceptibility to laryngeal squamous cell carcinoma (LSCC). OBJECTIVE: In this case-control study, the association of HO-1 microsatellite (GT)n repeat polymorphisms and serum levels with the risk of LSCC was investigated. METHODS: A total of 142 LSCC patients, 54 vocal leukoplakia patients and 98 healthy controls, were examined for (GT)n polymorphisms by sequencing, and the serum HO-1 levels were detected in a sub-set from participants above by ELISA. RESULTS: Compared with the controls, the LSCC group had significantly higher frequencies of L-allele (> 29 repeats) and L-allele carriers (p < 0.001, OR = 2.037 and p = 0.005, OR = 2.152, respectively). The frequencies of lymph node metastasis and of moderate or poor differentiation were significantly higher in L-allele carriers compared to non-L-allele carriers (p < 0.05). Significantly lower serum HO-1 levels were detected in LSCC patients (p < 0.001), and patients with lower serum HO-1 levels had more advanced cancer stage and a higher lymph node metastasis rate (p < 0.05). Furthermore, the L-allele carriers had lower serum HO-1 concentrations compared with the non-L-allele carriers (p = 0.019).

The ratio of CD4/CD8 T-cells in human papillomavirus-positive laryngeal squamous cell carcinoma accounts for improved outcome.

CONCLUSION: Improved prognosis associated with HPV-positive status may depend on lower CD4/CD8 ratio. Th1 CD4(+ )T cells were found to be the major sub-set of T lymphocytes in the HPV positive laryngeal squamous cell carcinoma microenvironment. BACKGROUND: To examine the prognostic significance of human papillomavirus (HPV) status in relation to the ratio of CD4/CD8 in LSCC. METHODS: In this study, 46 LSCC biopsy samples were retrospectively assessed using immunohistochemistry for CD4(+ )and CD8(+ )tumor infiltrating lymphocytes (TILs). HPV status was determined by HPV in situ hybridization (ISH) and p16(INK4A) immunohistochemistry. Of the 46 samples, 21 were evaluated for the expression of IFN-γ and IL-4 by quantitative real-time PCR (qRT-PCR). The influence of HPV status on locoregional tumor control and T-cell sub-sets infiltrating tumor microenvironment were investigated. RESULTS: Nineteen patients (41.3%) were classified as HPV positive, who had improved disease-free survival (28% in reduction, hazard ratio =0.10; 95% CI =0.011-0.938). A direct correlation between the HPV status and the ratio of CD4/CD8 or mean levels of CD8(+ )T cells was observed. Compared with the HPV-negative samples, HPV-positive samples had a higher ratio of IFN-γ/IL-4 (24.43 ± 29.89 vs 3.90 ± 4.03; p = 0.0375).

[Association of IL-10 promoter polymorphism and plasma levels with susceptibility to vocal cords leukoplakia].

OBJECTIVE: To investigated the association between interleukin-10(IL-10)-1082/-819/-592 promoter polymorphism, plasma IL-10 levels and risk of vocal leukoplakia. METHODS: A case-control study of 61 patients with vocal cords leukoplakia and 119 healthy subjects were performed. Genotypes for the IL-10 gene (IL-10 -1082 G/A, -819 C/T and -592 C/A) were determined using pyrosequencing and plasma IL-10 levels were analyzed by ELISA. RESULTS: Smoking and alcohol consumption increased the risk of vocal leukoplakia (OR = 4.73, 95%CI:2.4-9.1;OR = 5.70, 95%CI:2.9-11.2, P < 0.01) . Patients with vocal cord leukoplakia had significantly higher frequencies of AC at -592 and -819 (OR = 1.93, 95%CI:0.97-3.81, P = 0.05) and AG at -1082(OR = 2.14, 95%CI:0.87-5.27, P = 0.092) than control. Vocal leukoplakia patients had higher concentration of plasma IL-10 (21.6 ± 0.5) pg/ml (X(-) ± s) than controls (19.0 ± 1.1)pg/ml(t = 2.08, P = 0.043) and the haplotype containing the G allele was associated with higher plasma IL-10 concentrations (24.3 ± 5.7) pg/ml compared with the ATA haplotype(19.9 ± 4.7) pg/ml (t = -2.64, P = 0.008). CONCLUSIONS: IL-10-1082/-819/-592 promoter polymorphism and high concentration of plasma IL-10 are associated with vocal cord leukoplakia, and the concentration of plasma IL-10 is associated with the genotypes of IL-10 promoter polymorphism.