RESUMO
Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor of the upper aerodigestive tract. The loss and gain of miRNA function promote cancer development through various mechanisms. RNA sequencing (RNA-seq) and miRNAs sequencing data from the Cancer Genome Atlas (TCGA) was used to show the dysfunctional miRNAs microenvironment and to provide useful biomarkers for miRNAs therapy. Seven miRNAs were found to be independent prognostic factors of HNSCC patients in the training cohort. A total of 60 target genes for these miRNAs were predicted. Nine target genes (CDCA4, CXCL14, FLNC, KLF7, NBEAL2, P4HA1, PFKM, PFN2 and SEPPINE1) were correlated with patient's overall survival (OS) outcomes. We identified novel miRNAs markers for the prognosis of head and neck squamous cell carcinoma.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , MicroRNAs/genética , Idoso , Biomarcadores Tumorais/metabolismo , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Feminino , Filaminas/genética , Filaminas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Fosfofrutoquinase-1 Muscular/genética , Fosfofrutoquinase-1 Muscular/metabolismo , Inibidor 1 de Ativador de Plasminogênio/genética , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Pró-Colágeno-Prolina Dioxigenase/genética , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Profilinas/genética , Profilinas/metabolismoRESUMO
BACKGROUND: Survivin has been recently identified as a promising novel therapeutic target and prognostic marker in different types of cancer. Here we conducted a comprehensive meta-analysis to better clarify they the precise prognostic and diagnostic value of survivin in head and neck squamous cell carcinoma (HNSCC). METHODS: Database of PubMed (Medline), Embase, and Web of Science were systematically searched for related published literature up to September 2020. Pooled hazards ratios (HR) and related 95% confidence intervals (CI) were used to estimate the association of survivin expression and survival outcomes in HNSCC patients. RESULTS: Twenty eight studies with 4891 patients were finally included in this meta-analysis, the pooled analysis indicated that the survivin expression was significantly correlated with poorer overall survival (OS) (HR, 2.02; 95% CI, 1.65-2.47, P < 0.001), and poorer disease-free survival (DFS)/ disease-specific survival (DSS) (HR = 2.03, 95%CI: 1.64-2.52, P < 0.001; HR = 1.92, 95%CI: 1.41-2.60, P < 0.001, receptively). Similar results were observed in subgroup analysis stratified by different cancer types, such as laryngeal squamous cell carcinoma (LSCC) (HR = 1.35, 95%CI: 1.05-1.74, P < 0.001), oral squamous cell carcinomas (OSCC) (HR = 2.45, 95%CI: 1.89-3.17, P < 0.001), nasopharyngeal carcinoma (NPC) (HR = 2.53, 95%CI: 1.76-3.62, P < 0.001) and HNSCC (HR = 1.52, 95%CI: 1.25-1.86, P < 0.001). Furthermore, ethnicity-stratified analysis indicated that survivin was significantly associated with poorer OS among both Asian and Non- Asian HNSCC patients (HR = 2.16, 95%CI: 1.76-2.66; HR = 1.56, 95%CI: 1.33-1.82, respectively). CONCLUSIONS: Our results suggested that survivin is predictors of worse prognosis in HNSCC patients. Hence, survivin is a potential therapeutic target for HNSCC.
Assuntos
Biomarcadores Tumorais , Expressão Gênica , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Survivina/genética , Humanos , Grupos Populacionais , Prognóstico , Viés de Publicação , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnósticoRESUMO
Background: ß-Catenin has been recently identified as a promising novel therapeutic target and prognostic marker in different types of cancer. Here, we conduct a meta-analysis to better clarify the correlation between ß-Catenin expression and survival outcomes in nasopharyngeal carcinoma (NPC) patients. Patients/methods: Following the Preferred Reporting Items or Systematic Reviews Meta Analyses (PRISMA) 2020 guidelines, the PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were systematically searched for relevant studies to explore the prognostic significance of ß-Catenin in NPC. Pooled hazards ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the association of ß-Catenin expression with survival outcomes in NPC patients. Odd ratios (ORs) and 95% CIs for clinicopathological characteristics were also statistically analyzed. Results: Eight studies involving 1,179 patients with NPC were ultimately included in the meta-analysis. Pooled analysis indicated that elevated ß-Catenin expression was significantly associated with poor OS (HR = 2.45, 95% CIs: 1.45-4.16, p = 0.001) and poor DFS/PFS (HR 1.79, 95% CIs: 1.29-2.49, p = 0.000). Furthermore, ß-cadherin was signifcantly associated with higher TMN stages (OR = 5.10, 95% CIs 2.93-8.86, p = 0.000), clinical stages (OR = 5.10, 95% CIs 2.93-8.86, p = 0.000) and lymph node metastasis (LNM) (OR = 5.01, 95% CIs 2.40-10.44, p = 0.000). Conclusions: This study demonstrated that for NPC, patients with elevated ß-Catenin expression are more likely to have poor survival.
RESUMO
N6-methyladenosine (m6A) modifications play an essential role in tumorigenesis. These modifications modulate RNAs, including mRNAs and lncRNAs. However, the prognostic role of m6A-related lncRNAs in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Based on LASSO Cox regression, enrichment analysis, univariate and multivariate Cox regression analysis, a prognostic risk model, and consensus clustering analysis, we analyzed 12 m6A-related lncRNAs in HNSCC sample data from The Cancer Genome Atlas (TCGA) database. We found 12 m6A-related lncRNAs in the training cohort and validated them in all cohorts by Kaplan-Meier and Cox regression analyses, revealing their independent prognostic value in HNSCC. Moreover, ROC analysis was conducted, confirming the strong predictive ability of this signature for HNSCC survival. GSEA and detailed immune infiltration analyses revealed specific pathways associated with m6A-related lncRNAs. In this study, a novel risk model including twelve genes (SAP30L-AS1, AC022098.1, LINC01475, AC090587.2, AC008115.3, AC015911.3, AL122035.2, AC010226.1, AL513190.1, ZNF32-AS1, AL035587.1 and AL031716.1) was built. It could accurately predict HNSCC outcomes and could provide new therapeutic targets for HNSCC patients.
Assuntos
Adenosina/análogos & derivados , Neoplasias de Cabeça e Pescoço/diagnóstico , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Adenosina/metabolismo , Idoso , Estudos de Coortes , Biologia Computacional , Feminino , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Microambiente TumoralRESUMO
Head and neck squamous cell carcinoma is a malignant tumor of the upper aerodigestive tract. These RNA-binding proteins (RBPs) influence post-transcriptional in cells and regulate cell physiology, participate in regulating RNA stability, alternative splicing, translation, modification, localization, and apoptosis. We used RNA sequencing data from The Cancer Genome Atlas to display dysfunctional RBPs microenvironments and provide potential useful biomarkers for head and neck squamous cell carcinoma (HNSCC) diagnosis and prognosis. Six RBPs (DNMT1, PCF11, EIF5A2, RNASE10, PSMA6, and IGF2BP2) were selected as independent prognosis factors of HNSCC patients. The Kyoto Encyclopedia of Genes and Genomes were mainly enriched in RNA transport, Spliceosome, RNA degradation, mRNA surveillance pathway, and Epstein-Barr virus infection. cBioPortal results demonstrated that these six genes were altered in 150 samples out of 504 HNSCC patients (30%) and the amplification of IGF2BP2 was the largest frequent copy-number alteration. Based on the online database, we identified novel RBPs markers for the prognosis of HNSCC.
Assuntos
Neoplasias de Cabeça e Pescoço/genética , Proteínas de Ligação a RNA/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Biomarcadores Tumorais/genética , Humanos , PrognósticoRESUMO
This study aimed to develop a novel surgery classification for an endoscopic approach to middle ear cholesteatoma. We retrospectively analyzed the surgical approaches and outcomes of patients with middle ear cholesteatoma. Middle ear cholesteatoma surgeries were divided into four types and two special types as follows: type I, attic retraction pocket, which only requires tympanostomy tube placement or retraction pocket resection and cartilage reconstruction; type II, cholesteatoma which is limited to the attic or in which endoscopy can confirm complete removal of mastoid cholesteatoma lesions, including type II a, requiring only use of a curette, and type II b, requiring use of an electric drill or chisel; type III, cholesteatoma not limited to the attic, in which endoscopy cannot confirm complete removal of mastoid cholesteatoma lesions, requiring the combined use of endoscope and microscope to perform endoscopic tympanoplasty and "Canal Wall Up" mastoidectomy; type IV, extensive involvement of mastoid cavity cholesteatoma lesions and/or cases with a potential risk of complications, removal of which can only be performed under a microscope for "Canal Wall Down" mastoidectomy. In addition, there were two special types: "difficult external auditory canal" and congenital cholesteatoma in children. In our system, type I and type II middle ear cholesteatoma surgery was completely performed under an endoscope alone. However, estimating the extent of the lesions, determining the choice of mastoid opening and reestablishing ventilation are the key points for an endoscopic approach to middle ear cholesteatoma. The classification of endoscopic middle ear cholesteatoma surgery may benefit the selection of surgical indications.
Assuntos
Colesteatoma da Orelha Média/cirurgia , Procedimentos Cirúrgicos Otológicos/classificação , Criança , Colesteatoma da Orelha Média/patologia , Meato Acústico Externo/cirurgia , Endoscopia , Feminino , Humanos , Masculino , Mastoidectomia/instrumentação , Procedimentos Cirúrgicos Otológicos/instrumentação , Estudos Retrospectivos , Resultado do Tratamento , Timpanoplastia/instrumentaçãoAssuntos
Implante Auditivo de Tronco Encefálico/métodos , Neurofibromatose 2/cirurgia , Idoso , Implante Auditivo de Tronco Encefálico/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurofibromatose 2/diagnóstico , Neurofibromatose 2/reabilitação , Percepção da Fala , FonoterapiaRESUMO
OBJECTIVE: To investigate the neurotoxicity and its mechanism of quinolinic acid (QA) to spiral ganglion cells (SGC) and observe the protectable potential of MgCl(2) on SGC. METHODS: SGC were cultured in vitro for 72 h, and then were divided into 4 groups: control group, QA group (1 mmol/L QA), MK-801 group (1 mmol/L QA + 20 µmol/L MK-801)and MgCl(2) protected group (1 mmol/L QA + 1 mmol/L MgCl(2)). SGC apoptosis rate was analyzed by Annexin V staining and PI staining measurements after 24 h exposure to different medium. SGC cultured as methods above were divided into 4 groups as following: 100 µmol/L QA, 1 mmol/L QA, 20 µmol/L MK-801+1 mmol/L QA and 1 mmol/L MgCl(2) + 1 mmol/L QA. The intracellular calcium concentration was measured by laser scanning confocal microscope finally. RESULTS: Apoptosis rate in QA group was higher than that in both of control group (59.1% ± 7.5% vs 9.2% ± 0.9%, x ± s, q = 11.9, P < 0.05) and MgCl(2) group (59.1% ± 7.5% vs 27.5% ± 8.3%, q = 7.5, P < 0.05). There was no significant difference between apoptosis rate of control and MK-801 group (12.8% ± 5.7% vs 9.2% ± 0.9%, q = 0.9, P > 0.05). It was shown that there was a significant increase of Ca(2+) in SGC in the presence of QA by laser scanning confocal microscope. MK-801 may completely block the increase of Ca(2+), and the increase of Ca(2+) can be reduce by the application of MgCl(2). CONCLUSIONS: QA might injure SGC by excessive activating NMDA receptors on the cell membrane. Mg(2+) may have the function to reduce the neurotoxicity of QA.
Assuntos
Neurotoxinas/toxicidade , Ácido Quinolínico/toxicidade , Gânglio Espiral da Cóclea/efeitos dos fármacos , Gânglio Espiral da Cóclea/metabolismo , Animais , Cálcio/análise , Células Cultivadas , Cloreto de Magnésio/farmacologia , Ratos , Ratos Sprague-Dawley , Gânglio Espiral da Cóclea/citologiaRESUMO
Both reinnervated and dormant neurons can be observed in facial nucleus following facial-facial anastomosis. Although they may play different roles in the remodeling mechanism of facial nucleus during facial nerve injury and regeneration, comprehensive gene profiling analysis of these two neuron types has never been performed due to the difficulty in isolating specific neuron populations and extracting sufficient amount of RNAs from the heterogeneous facial nucleus. In this study, we developed a method to isolate the Fluoro-Ruby (FR) retrogradely labeled reinnervated facial motor neurons and the Nissl stained dormant neurons in two steps with laser capture microdissection (LCM) technology. The quality and yield of RNAs extracted from these isolated neurons were confirmed with Agilent 2100 Bioanalyzer. This modified LCM based neuron isolation method will facilitate the studies of the roles and interactions of different neurons that co-exist in the same facial nucleus after peripheral injury.
Assuntos
Nervo Facial/citologia , Neurônios Motores/química , RNA/isolamento & purificação , Anastomose Cirúrgica , Animais , Lasers , Masculino , Microdissecção , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To explore the clinical significance and surgical technique for revisionary submucous resection of nasal septum. METHODS: Thirty-two patients who had undergone nasal septal resection were evaluated rhinologically and the causes of unsuccessful septoplasty were analysed . Based on the location and extent of deviation, the status of residual cartilage and bone, and the age of the patients, one of three incisions was chosen during septal surgeries: (1) For 5 cases with anterior, 1 with inferior and 14 with superior deviation, a "U" shaped incision at the left side of anterior edge of septum cartilage was used. (2) For 8 cases with posterior and 2 with superior deviation, the site of the incision was located just anterior to the deviation, with the aid of endoscope. (3) For 2 cases with anteroinferior deviation, because of their young age, a sublabial incision was made to surge the mucosa of the septum and base of nasal cavity, the otological electronic drill was then used. RESULTS: Revision nasal septoplasty was successful in all cases. The symptoms resulting from septal deviation disappeared or significantly relieved. Following successful revision surgery, the treatment outcomes of concomitant nasal and/or sinusal diseases also significantly improved. CONCLUSION: Revision nasal septoplasty requires different approaches depending on different clinical characteristics. A successful correction of septal deviation can not only relieve the symptoms derived from deviation, but also be of significance for the treatment of concomitant nasal and/or sinusal diseases.