Noninvasive prognostic factors and web predictive tools for idiopathic sudden sensorineural hearing loss.

PURPOSE: To friendly predict a reference prognostic outcome for idiopathic sudden sensorineural hearing loss (ISSNHL) patients with or without anxiety, we identified independent prognostic factors and developed practical predictive tools without invasive tests. METHODS: Patients with ISSNHL in our center were enrolled from June 2013 to December 2018. Univariate and multivariate logistic regression analyses were performed to identify independent prognostic factors of the complete recovery and the overall recovery for ISSNHL, which were subsequently utilized to develop the web nomograms. The discrimination, calibration, and clinical benefit were used to evaluate the performance of nomograms for ISSNHL. RESULTS: 704 ISSNHL patients were finally enrolled in this study. Multivariate logistic regression analysis showed that age, time of onset, gender, affected ear, degree, and type of hearing loss were independent prognostic factors of complete recovery. Age, time of onset, affected ear, and type of hearing loss were independent prognostic factors of overall recovery. Web predictive nomograms were developed with excellent discrimination, calibration, and clinical value. CONCLUSION: Based on the patients' data with a considerable size, independent noninvasive prognostic factors of complete recovery and overall recovery of ISSNHL were identified. Integrating these prognostic factors without invasive tests, practical web predictive nomograms were developed. Using web nomograms, clinical doctors could provide reference data (the predicted recovery rate) for supporting prognostic consultation of ISSNHL patients, especially those with anxiety.

Identification and validation of ferroptosis-related genes for chronic rhinosinusitis with nasal polyps.

PURPOSE: Even though the great progress in the field of chronic rhinosinusitis with nasal polyps (CRSwNP) has been achieved, ferroptosis and its molecular mechanism in CRSwNP remain blank. We are the first to study the relationship between CRSwNP and ferroptosis, aiming to identify ferroptosis-related genes in the process of CRSwNP. METHODS: Using the GEO database and the FerrDb database, significantly differentially expressed ferroptosis-related genes (DEFGs) were selected between CRSwNP-NP and CRSwNP-IT specimens. Then, the protein-protein interaction (PPI) network of ferroptosis-related genes was constructed. Functional enrichment analyses (GSVA, GO, KEGG, and GeneCodis analyses) were introduced in our study. Besides, based on the GSE136825 data set, DEFGs between CRSwNP-NP and CS-IT specimens were also analyzed. Finally, qRT-PCR was performed to validate the selected ferroptosis-related genes with clinical samples. RESULTS: 31 significantly DEFGs were identified between CRSwNP-NP and CRSwNP-IT specimens. Functional enrichment analyses and the analysis of GeneCodis 4 pointed out that DEFGs may potentially be involved in some related KEGG pathways. 8 DEFGs were selected between CRSwNP-NP and CS-IT specimens. The experimental verification indicated that 4 genes (GPX2, CDO1, CAV1, and TP53) were the important DEFGs of CRSwNP. The Venn diagrams proved that CDO1 and GPX2 were considered as the most important DEFGs genes of CRSwNP, especially GPX2. CONCLUSIONS: Though a comprehensive bioinformatics analysis and the experimental verification, CDO1 and GPX2 were considered as the important ferroptosis-related genes of CRSwNP, especially GPX2. However, further molecular biological experiments would be still required to uncover the underlying mechanism between ferroptosis and CRSwNP.

The causal association between peripheral blood eosinophils and nasal polyps: a Mendelian randomization study.

OBJECTIVE: Observational studies suggested that peripheral blood eosinophils were associated with the risk of nasal polyps. However, these studies did not confirm the causality. This study aims to apply Mendelian randomization (MR) method to comprehensively assess the potential causal association between peripheral blood eosinophils and nasal polyps. METHODS: Genetic instrumental variables were extracted from the largest available genome-wide association study (GWAS) of European participants, which were used to investigate the relationship between peripheral blood eosinophils and nasal polyps. The inverse variance weighted method, the MR Egger method, and the weighted median method were applied for this analysis. MR-Egger intercept tests, leave-one-out analyses, and funnel plots were performed for the sensitivity analysis. RESULTS: With the inverse variance weighted method, the MR analysis suggested that there was a significant difference between peripheral blood eosinophils and the risk of nasal polyps (ukb-a-97, OR 1.004, 95% CI 1.003-1.005, p < 0.001; ukb-a-541, OR 1.005, 95% CI 1.004-1.006, p < 0.001; ukb-b-7211, OR 1.004, 95% CI 1.003-1.005, p < 0.001; ukb-b-8425, OR 1.004, 95% CI 1.003-1.005, p < 0.001; finn-b-J10_NASALPOLYP, OR 3.089, 95% CI 2.537-3.761, p < 0.001). Consistent results were also proved by using the weighted median method and the MR Egger method. CONCLUSIONS: Our findings reveal the causal effect of peripheral blood eosinophils on the increased risk of nasal polyps.

Prognostic factors and a dynamic model on cancer-specific survival for T1a N0 M0 glottic cancer: A population-based analysis and clinical validation.

OBJECTIVES: The survival rate varies tremendously in T1a N0 M0 glottic cancer patients, which may be associated with the difference on patients' characters, such as age, treatment, and marital status. The objective of this study is to identify the vital factors and construct a dynamic prognostic model for predicting the cancer-specific survival (CSS) of patients with T1a N0 M0 glottic cancer. DESIGN, SETTING, AND PARTICIPANTS: The data of T1a N0 M0 glottic cancer patients were extracted retrospectively from the SEER database between 2004 and 2015, which were randomly divided into the training dataset (70%) and the validation dataset (30%). The training cohort was used to identify independent prognostic factors and build the prognostic nomogram. While the validation cohort was used to validate the applicability of the newly constructed model. MAIN OUTCOME MEASURES: The model was evaluated with the discrimination, the calibration, and the clinical benefit. The external data collecting from a medical center were used to validate the performance of the prognostic model. RESULTS: Totally, 3286 eligible patients in the data of the SEER database and 139 eligible patients in our external clinical cohort were finally identified. 5 independent prognostic factors (age, marital status, Grade, primary site surgery, and chemotherapy) were identified and applied to develop the dynamic prognostic tool. C-indexes, receiver operating characteristic curves, calibration curves, and decision curve analyses proved that the prognostic nomogram showed excellent predictive accuracy, ability, and prognostic value. Using internal and external cohorts, the validation of the model also proved its reliability. CONCLUSION: Prognostic factors for T1a N0 M0 glottic cancer were identified. The novel web-based prognostic prediction tool may be beneficial in clinical decision-making and has value in risk stratification, personalized treatment, and clinical trial design.

Novel predictive tools and therapeutic strategies for patients with initially diagnosed glottic cancer in the United States.

OBJECTIVE: The objective of this study is to identify valuable prognostic factors, build clinical prediction nomograms, and recommend the optimal therapeutic strategy for patients with initially diagnosed glottic cancer. METHODS: Patients were extracted from the SEER database. Cox regression analyses, survival analyses, an internal validation, the propensity score analysis, and the competing risk analysis were performed. RESULTS: Nine overlapped factors were considered as valuable prognostic factors. Furthermore, nomograms were established for clinical prediction models to assess the 1-, 3-, and 5-year overall survival (OS) and cancer-specific survival (CSS). C-indexes, receiver operating characteristic curves, calibration curves, and decision curve analyses proved that nomograms showed better predictive accuracy, ability, and prognostic value compared to the American Joint Committee on Cancer stage. For patients in stage I, primary site surgery alone would acquire best OS and CSS. For patients in stage II, primary site surgery and/or radiation would gain better OS and CSS. For patients in stage III, radiation plus chemotherapy or primary site surgery (alone or plus radiation) would acquire better OS and CSS. Moreover, for patients in stage IV, primary site surgery plus radiation would gain better OS and CSS. CONCLUSIONS: Nomograms could be useful for patients' counseling and guide therapeutic decision-making. Primary site surgery alone may likely be the optimal therapy for stage I glottic cancer, and primary site surgery and/or radiation may be the recommended therapy for stage II glottic cancer. The combination treatment would be the preferred choice for advanced-stage (stage III & IV) glottic cancer, and the role of chemotherapy needs to be further explored.

A comparison of the survival between laser surgery and radiation in T1aN0M0 glottic cancer: a population-based analysis and meta-analysis.

OBJECTIVE: The objective of this study is to compare the overall survival (OS) and the cancer-specific survival (CSS) for patients of T1aN0M0 glottic cancer who underwent laser surgery (LS) or radiation (RT). METHODS: The data of the population-based analysis were extracted from the SEER database. The studies of the meta-analysis were identified through PubMed, EMBASE, and Cochrane databases. Cox regression analyses, the propensity score analysis (PSM), survival analyses, and the meta-analysis were performed. RESULTS: In the population-based analysis, 2101 eligible patients were included. Multivariable Cox analyses indicated that patients accepting LS alone would obtain better OS (HR 0.77, 95% CI 0.61-0.98, p = 0.03) and CSS (HR 0.26, 95% CI 0.12-0.59, p = 0.001) than those of whom they accepted RT alone. Survival analyses before PSM and after PSM also indicated that patients who underwent LS alone would have better OS and CSS. In the meta-analysis, nine eligible studies were included. Results of the pooled effect showed that significant differences existed between LS and RT groups on OS (OR: 1.84, 95% CI 1.36-2.50, p < 0.001) and CSS (OR 3.84, 95% CI 1.17-12.52, p = 0.026), both distinctly favoring LS. CONCLUSIONS: Compared with RT, LS may acquire better survivals for patients with T1aN0M0 glottic cancer. Simultaneously, more multi-center randomized controlled trials would be warranted to prove the conclusion.

Prognostic risk factors for initially diagnosed T2N0M0 glottic cancer: competing risk analysis and propensity-score matched cohort analysis.

BACKGROUND: Prognostic risk factors of patients with initially diagnosed T2N0M0 glottic cancer remain unclear. This study was aimed to conduct a comprehensive analysis to identify valuable prognostic risk factors for initially diagnosed T2N0M0 glottic cancer. METHODS: Data of patients with initially diagnosed T2N0M0 glottic cancer were extracted from the Surveillance, Epidemiology, and End Results database. Survival analyses and Cox regression analyses were conducted to evaluate overall survival (OS) and cancer-specific survival (CSS). In consideration of competing events, the competing risk (CR) analysis was applied. Furthermore, propensity-score matching (PSM) was applied to mimic randomized-controlled trials and reduce selection bias. RESULTS: A total of 923 eligible patients met the inclusion criteria. Survival analyses showed that age, marital status, primary site surgery, and radiation were independent predictors of OS. Besides, age, marital status, primary site surgery, radiation, and chemotherapy were independent predictors of CSS. Cox regression analyses and the CR analysis were basically consistent with this result. In addition, an internal validation and PSM were performed to explore the role of chemotherapy. CONCLUSION: We conducted a comprehensive analysis to prove that age, marital status, primary site surgery, radiation, and chemotherapy may be valuable prognostic risk factors for initially diagnosed T2N0M0 glottic cancer. Primary site surgery and radiation should be recommended, whereas chemotherapy was likely not suitable so far. Furthermore, we constructed a CR nomogram to predict survival rates.

Identification of core miRNA prognostic markers in patients with laryngeal cancer using bioinformatics analysis.

PURPOSE: Lots of studies indicated that many microRNAs (miRNAs) are associated with the prognosis of patients with laryngeal cancer (LC). The objective of our study is to identify potential core miRNAs associated with the pathogenesis and prognosis of LC. METHODS: Using the Cancer Genome Atlast database, we identified 70 differentially expressed miRNAs between LC tumor specimens and non-tumor specimens. Then Cox regression analyses and the least absolute shrinkage and selection operator regression signature were performed to detect miRNA prognostic markers. A nomogram integrating miRNA prognostic markers was constructed to predict overall survival (OS) for LC patients. The potential target genes of the key miRNA were predicted by miRTarBase and miRDB databases. Subsequently, their potential functions were revealed by gene ontology annotation and kyoto encyclopedia of genes and genomes pathway enrichment analysis. Related biological pathways of the key target gene involved in LC were detected through gene set enrichment analysis (GSEA). RESULTS: A prognostic miRNA signature was constructed. The up-regulated miR-105-1 was related to a worse OS (p = 0.043), which suggested that miR-105-1 may likely be the key miRNA prognostic marker. Survival analyses and paired expression analyses of target genes indicated that ENDOU may be the key target gene. Finally, we conducted GSEA to elucidate the pathways enriched between low- and high-ENDOU expression datasets. CONCLUSION: Our findings might bring some new light on the pathogenesis of LC. Then, it might facilitate doctors to predict the prognosis and improve treatment outcomes for LC patients. However, the behaviors of LC are relatively heterogeneous, and the TCGA database cannot provide detailed information about the subsites and treatment modalities of LC. Further molecular biological experiments and clinical investigations would be required to confirm this conclusion.

MiRNA-mRNA crosstalk in laryngeal squamous cell carcinoma based on the TCGA database.

BACKGROUND: The functional characterization of non-coding microRNAs (miRNAs) has been shown to be associated with the pathophysiology of the disease, but it is still a challenging task to elucidate the pathogenesis of microRNAs and disease. In addition, the understanding of the role of miRNAs in the development of LSCC still needs further exploration. MATERIALS AND METHODS: In this study, to identify miRNAs that play a key role in LSCC, we analyzed miRNA and mRNA sequence data from 162 LSCC samples from the TCGA database, and screened specific miRNAs and mRNAs by differential gene expression analysis. And then, construct a differentially expressed miRNAs and mRNAs interaction network. RESULTS: In our investigation, 23 miRNAs (P < 0.01, log2FoldChange > 2) and 331 mRNAs (P < 0.01, log2FoldChange > 4) were identified differentially expressed in LSCC and reduced the number of loosely linked miRNAs and mRNAs according to appropriate thresholds. Finally, 13 miRNAs and 35 mRNAs were enriched in a network. CONCLUSIONS: Our study provides the most comprehensive information on the expression of miRNAs in LSCC and identifies the known oncogenic miRNAs (such as miR-163a), as well as aberrant expression of novel miRNAs involved in cell regulation and metabolic defects that occur during development of LSCC.