Prognostic Correlation of Glycolysis-Related Gene Signature in Patients with Laryngeal Cancer.

BACKGROUND: Aerobic glycolysis is one of the metabolic characteristics of tumor cells, which is regulated by many genes. The aim of our study was to construct glycolysis-related gene signature to accurately predict the prognosis of laryngeal cancer (LC) patients. METHODS: We analyzed the mRNA expression profiles of LC patients from The Cancer Genome Atlas (TCGA). Eleven glycolysis-related gene sets were analyzed by gene set enrichment analysis (GSEA). In order to acquire the gene signature related to prognosis, we used univariate and multivariate Cox regression analysis. RESULTS: We confirmed that a gene signature composed of two genes (STC2, LHPP) can predict the overall survival (OS) of patients with LC. Based on each patient's risk score, we found that the survival results of patients in the high-risk group were significantly lower than those in the low-risk group (log-rank test P-value=0.002). Multivariate Cox regression analysis confirmed that gene signature could independently predict OS in LC patients (HR = 1.981, 95% CI 1.446-2.714 P<0.001). In addition, a nomogram including the age, sex, grade and risk score was constructed. The nomogram demonstrated good accuracy for OS prediction, with a C-index of 0.752. CONCLUSION: The glycolysis-related two-gene risk score model could be used as a biomarker for LC prognosis.

Downregulation of miR­29b­3p promotes α­tubulin deacetylation by targeting the interaction of matrix metalloproteinase­9 with integrin ß1 in nasal polyps.

Matrix metalloproteinase (MMP)­9 is a key enzyme responsible for extracellular matrix degradation and contributes to the progressive histological changes observed in lower respiratory tract infections. Integrin ß1 and α­tubulin are potential MMP­9­interacting proteins, and microRNA (miR)­29b­3p can regulate MMP­9 expression. MMP­9 is highly expressed in chronic rhinosinusitis with nasal polyps (CRSwNPs), regardless of its effects on miR­29b­3p, integrin ß1 and α­tubulin expression. In the present study, samples from 100 patients with CRSwNPs were examined via reverse transcription­quantitative PCR to assess the mRNA expression of miR­29b­3p, and western blotting was performed to assess the protein expression of MMP­2, MMP­9, acetyl­α­tubulin, integrin ß1 and tissue inhibitor of metalloproteinase 1 (TIMP­1). A dual­luciferase reporter assay was used to verify the direct binding of miR­29b­3p and MMP­2/MMP­9. Co­immunoprecipitation (Co­IP) and GST pull­down assays showed that integrin ß1 and α­tubulin were MMP­9­interacting proteins. Cell viability, apoptosis and inflammatory cytokine levels were determined via a Cell Counting Kit­8 assay, flow cytometry and ELISA, respectively. miR­29b­3p expression was found to be positively correlated with MMP­2 and MMP­9 expression. Whereas, TIMP­1 expression was negatively correlated with MMP­2 and MMP­9 expression. The dual­luciferase assay revealed that miR­29b­3p targeted the 3' untranslated region of MMP­2/MMP­9. The Co­IP and GST pull­down assays showed that MMP­9 could directly bind to integrin ß1 and indirectly bind to α­tubulin. Finally, the overexpression of miR­29b­3p decreased the expression of MMP­9 and increased the levels of acetyl­α­tubulin. By contrast, the knockdown of miR­29b­3p increased the expression of MMP­9 and decreased the levels of acetyl­α­tubulin. Additionally, MMP­9 expression was found to be negatively correlated with acetyl­α­tubulin expression. Of note, the expression of integrin ß1 did not change following the overexpression and knockdown of MMP­9. Finally, the overexpression of miR­29b­3p not only decreased MMP­9 expression, but also alleviated lipopolysaccharide­induced inflammation in NP69 cells. The results showed that the downregulation of miR­29b­3p promoted α­tubulin deacetylation by increasing the number of MMP­9­integrin ß1 complexes in CRSwNPs, thus targeting miR­29b­3p/MMP­9 may be a potential novel strategy for the clinical treatment of CRSwNPs.

Development and validation of a hypoxia-related gene pair signature to predict overall survival in head and neck squamous cell carcinoma.

OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) are a highly aggressive tumor with an extremely poor prognosis. Thus, we aimed to develop and validate a robust prognostic signature that can estimate the prognosis for HNSCC. METHODS: Data on gene expressions and clinical were downloaded from TCGA and GEO database. To develop the best prognosis signature, a LASSO Cox Regression model was employed. Time-dependent receiver-operating characteristic (ROC) was used to determine the best cut-off value. Patients were divided into high-risk and low-risk hypoxia groups according to cut-off value. Survival differences were evaluated by log-rank test, while multivariate analysis was performed by a Cox proportional hazards model. RESULTS: A 17-HRGPs composed of 24 unique genes was constructed, which was significantly related to OS. In the TCGA and GEO datasets, patients in the high hypoxia risk group have a poor prognosis (TCGA: P < 0.001, GEO: P < 0.05). After adjusting for other clinicopathological parameters, the 17-HRGP signature was independent prognostic factors in patients with HNSCC (P < 0.05). Functional analysis revealed that mRNA binding, gene silencing by RNA, RNA binding involved in posttranscriptional gene silencing signaling pathway were enriched in the low-risk groups. For this model, C-index was 0.684, which was higher than that of many established risk models. Macrophages M0, Mast cells activated, NK cells resting, T cells CD4 memory resting, etc. were significantly higher in the high-risk group, and B cells memory, Plasma cells, T cells follicular helper, T cells gamma delta, T cells CD8, etc. were significantly higher in the low-risk group. CONCLUSION: In summary, our study constructed a robust HRGPs signature as molecular markers for predicting the outcome of HNSCC patients.

Effects of marital status on overall and cancer-specific survival in laryngeal cancer patients: a population-based study.

Marital status has long been recognized as an important prognostic factor for many cancers, however its' prognostic effect for patients with laryngeal cancer has not been fully examined. We retrospectively analyzed 8834 laryngeal cancer patients in the Surveillance Epidemiology and End Results database from 2004 to 2010. Patients were divided into four groups: married, widowed, single, and divorced/separated. The difference in overall survival (OS) and cancer-specific survival (CSS) of the various marital subgroups were calculated using the Kaplan-Meier curve. Multivariate Cox regression analysis screened for independent prognostic factors. Propensity score matching (PSM) was also conducted to minimize selection bias. We included 8834 eligible patients (4817 married, 894 widowed, 1732 single and 1391 divorced/separated) with laryngeal cancer. The 5-year OS and CSS of married, widowed, single, and separated/divorced patients were examined. Univariate and multivariate analyses found marital status to be an independent predictor of survival. Subgroup survival analysis showed that the OS and CSS rates in widowed patients were always the lowest in the various American Joint Committee on Cancer stages, irrespective of sex. Widowed patients demonstrated worse OS and CSS in the 1:1 matched group analysis. Among patients with laryngeal cancer, widowed patients represented the highest-risk group, with the lowest OS and CSS.