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1.
Laryngoscope ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33592124

RESUMO

OBJECTIVE/HYPOTHESIS: Hepatitis C virus (HCV) was reported to associate with head and neck squamous cell carcinoma (HNSCC) in many studies. However, its correlation with prognosis of non-human papillomavirus (HPV) associated HNSCC remains unknown. Here, we sought to investigate clinical significance of HCV RNA transcript in non-HPV associated HNSCC by analyzing corresponding RNA-seq data. STUDY DESIGN: A retrospective cohort study. METHODS: Four hundred and forty-eight non-HPV associated HNSCC patients with aligned RNA-seq and clinical follow-up data were included and divided into two groups: low-HCV and high-HCV. Means of continuous variables and proportions of categorical variables were compared using independent sample t-test and chi-square test, respectively. Survival data were compared using Cox regression analysis, Kaplan-Meier curves, and log-rank test. Expression of genome-wide mRNAs and abundance of immune cells were compared using volcano plot and cell signature estimated score analysis. RESULTS: HCV RNA transcript negatively correlates with pathologic (P = .028) and clinical-stage (P = .023), clinical N stage (P = .025), and nodal extracapsular spread (P = .042) and is an independent prognosis factor in non-HPV associated HNSCC (HR = 1.488; 95% CI: 1.004-2.206; P = .048). Elevated expression of HCV improved 5-year overall survival (43.6% vs. 53.2%; P = .035) in all non-HPV associated HNSCC patients, the same as in male (46.6% vs. 58.7%; P = .049), clinical M0 stage (42.8% vs. 52.9%; P = .036), white (42.9% vs. 55.9%; P = .010), and histologic grade 1 to 2 subgroups (42.1% vs. 57.2%; P = .043). The expression of several immune-related genes and abundance of some immune cells significantly changed with the increase of HCV RNA transcript, while HCV-related oncogenes and tumor suppressor gene did not. CONCLUSIONS: HCV RNA transcript is an independent favorable factor for prognosis of non-HPV associated HNSCC. LEVELS OF EVIDENCE: 4 Laryngoscope, 2021.

2.
Sci Rep ; 10(1): 19459, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33173143

RESUMO

The link between differences in molecular expression and survival among advanced laryngeal (LSCC) and hypopharyngeal squamous carcinoma (HPSCC) remains unclear. Here, we applied the Surveillance, Epidemiology, and End Results (SEER) program, Isobaric tag for relative and absolute quantitation (iTRAQ) with Liquid chromatography-mass spectrometry (LC-MS/MS) proteomics data and The Cancer Genome Atlas (TCGA) related data to discover the possible disparities between HPSCC and LSCC. Our results showed a significantly worse 5-year overall-survival in HPSCC compared with LSCC before and after adjusting for clinical parameters. 240 differentially expressed proteins were enriched in molecular networks of cytoskeleton remodeling and antigen presentation. Moreover, HPSCC consisted of less T-central-memory cells, T-follicular-helper cells, TGF-ß response, and CD4 +  T memory resting cells, but more wound healing than LSCC. Furthermore, 9 mRNAs expression were  significantly and independently correlated to overall survival in 126 HPSCC and LSCC patients, which was further validated in another cohort of head and neck cancers. These findings support that Immunity signatures as well as pathway networks that include cytoskeleton remodeling and antigen presentation may contribute to the observed differences in survival between HPSCC and LSCC.

3.
Artigo em Chinês | MEDLINE | ID: mdl-32791602

RESUMO

Sensory laryngeal neuropathy(SLN) is a kind of peripheral neuropathy presenting globus pharyngeus, chronic cough, increased mucus, dry throat, sore throat, frequent clearing of the throat, etc. When the sensory nerve of the larynx is affected by chemical, biological, mechanical or nutritional factors. Because of its nonspecific signs and symptoms, SLN is easy to be misdiagnosed as chronic pharyngitis or laryngopharyngeal reflux disease. SLN was came up to ENT physician in recent years and there are rare systematic reports currently, therefore, this review aims to summarize the etiology, clinical manifestations, diagnosis and treatment of SLN, to raise awareness of this disease among our colleagues.


Assuntos
Doenças da Laringe , Refluxo Laringofaríngeo , Laringe , Doenças do Sistema Nervoso Periférico , Tosse , Humanos , Faringe
4.
Laryngoscope ; 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32297993

RESUMO

OBJECTIVES/HYPOTHESIS: To investigate differences in the immunogenomic landscape among young patients presenting with oral cavity squamous cell carcinoma (OCSCC). STUDY DESIGN: Retrospective database review. METHODS: Normalized messenger mRNA expression data were downloaded from The Cancer Genome Atlas (TCGA) database. OCSCC patients were categorized into young and older age groups with a cutoff of 45 years. Human papillomavirus-positive tumors were excluded. Cell fractions, marker expression, and mutational load were compared between age groups using the Wilcoxon rank sum test. Adjustment for multiple comparisons was performed using the Benjamini-Hochberg method, with a false discovery rate of 0.05. RESULTS: Two hundred forty-five OCSCC tumors were included; 21 (8.6%) were young (37.1 ± 7.5 years) and 224 (91.4%) were older (64.5 ± 10.3 years). There was no significant difference between groups in the fraction of B and T lymphocytes, macrophages, monocytes, natural killers, and dendritic cells. Cytolytic activity score was decreased in young patients (8.33 vs. 18.9, P = .023). Additionally, young patients had significantly lower expression of immunomodulatory markers of immune activation, including PD-1 (PDCD1, P = .003), CTLA4 (P = .025), TIGIT (P = .002), GITR (TNFRSF18, P = .005), OX40 (TNFRSF4, P = .009), LAG-3 (P < .001), and TIM-3 (HAVCR2, P = .002). Young patients had a significantly lower number of single nucleotide variant-derived neoantigens (26.2 vs. 60.6, P < .001). CONCLUSIONS: OCSCC patients aged 45 years and younger appear to have an attenuated immune response that may be related to a lower frequency of immunogenic mutations. This may contribute to the pathogenesis of these tumors, and ultimately help inform personalized immune-based therapeutic strategies for young patients with OCSCC. LEVEL OF EVIDENCE: NA Laryngoscope, 2020.

5.
Front Oncol ; 10: 87, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32117741

RESUMO

Alternative splicing (AS) is an important mechanism that is responsible for the production of protein diversity. An increasing body of evidence has suggested that out-of-control AS is closely related to the genesis and development of cancer. Systematic analysis of genome-wide AS in head and neck squamous cell carcinoma (HNSCC) has not yet been carried out, and consideration of this topic remains at the preliminary stage and requires further investigation. In this study, systemic bioinformatic analysis was carried out on the genome-wide AS events of 555 clinical HNSCC samples from the TCGA database. Firstly, we statistically analyzed the distributions of seven AS event types in HNSCC samples. Then, through univariate survival analysis, we observed the relationship between AS and the prognosis of the disease and found that 437 intersections of AS events were significantly related to overall survival. Among them, 335 cross-genes showed a high degree of consistency in the genes associated with overall survival and recurrence. The overall survival was significantly related to AS events. Besides, the frequency of overall survival-related ES events was evidently reduced, while the AP and the AT events were increased. In addition, AT events accounted for the largest proportion. Further, multiple regression model analysis proved that AS could become a new classification method for HNSCC, and KEGG enrichment analysis proved that most genes and proteins interacting with AS events had different biological functions and were associated with a variety of diseases. Finally, through the selection of characteristic HNSCC genes and the construction of a prognostic model, seven cross-genes related to survival and recurrence were screened out, and these characteristic genes were verified by multivariate survival model analysis so as to classify the prognosis at different splicing times and gene expression levels. These results have laid a solid foundation for our further research and play a decisive role in showing the correlation of AS with the prognosis of HNSCC.

6.
Mol Genet Genomics ; 295(3): 675-684, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32002629

RESUMO

Laryngeal papillomas (LP) is a difficult disease to manage due to its frequent recurrence, airway compromise, and risk of cancer. Recently, growing evidence indicates the aberrant expression of OGFPD1, a stress granule protein, links closely to the development of tumorigenesis; however, little is known about its role in LP progression. Here, we investigated the tumor promoting action of OGFOD1 in LP. The transcriptional and translational levels of OGFOD1 were significantly up-regulated in LP tissues and cells. Moreover, OGFOD1 promoted viability and proliferation, and inhibited LP cells apoptosis. We further revealed that OGFOD1 was directly targeted by miR-1224-5p, which was significantly down-regulated in LP. Overexpression of the miR-1224-5p suppressed OGFOD1-induced cell proliferation and viability, and promoted apoptosis of LP. In accordance, knockdown of miR-1224-5p inversed the inhibitory effects. In confederation of the central involvement of OGFOD1 in LP progression, targeting the miR-1224-5p/OGFOD1 pathway might provide a novel strategy for LP treatment.


Assuntos
Proteínas de Transporte/metabolismo , Proliferação de Células , Neoplasias Laríngeas/patologia , MicroRNAs/genética , Proteínas Nucleares/metabolismo , Papiloma/patologia , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Apoptose , Proteínas de Transporte/genética , China/epidemiologia , Regulação Neoplásica da Expressão Gênica , Humanos , Incidência , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/virologia , Proteínas Nucleares/genética , Papiloma/epidemiologia , Papiloma/virologia , Infecções por Papillomavirus/virologia , Células Tumorais Cultivadas
7.
Aging (Albany NY) ; 12(1): 767-783, 2020 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-31927533

RESUMO

The prognosis of head and neck squamous cell carcinoma (HNSCC) patients remains poor. High-throughput sequencing data have laid a solid foundation for identifying genes related to cancer prognosis, but a gene marker is needed to predict clinical outcomes in HNSCC. In our study, we downloaded RNA Seq, single nucleotide polymorphism, copy number variation, and clinical follow-up data from TCGA. The samples were randomly divided into training and test. In the training set, we screened genes and used random forests for feature selection. Gene-related prognostic models were established and validated in a test set and GEO verification set. Six genes (PEX11A, NLRP2, SERPINE1, UPK, CTTN, D2HGDH) were ultimately obtained through random forest feature selection. Cox regression analysis confirmed the 6-gene signature is an independent prognostic factor in HNSCC patients. This signature effectively stratified samples in the training, test, and external verification sets (P < 0.01). The 5-year survival AUC in the training and verification sets was greater than 0.74. Thus, we have constructed a 6-gene signature as a new prognostic marker for predicting survival of HNSCC patients.

8.
Laryngoscope ; 130(5): 1349-1356, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31508818

RESUMO

OBJECTIVE: To analyze the effect of drain placement on postoperative hematoma formation and other associated outcomes post-thyroid surgery in a large national cohort. METHODS: This was a retrospective study that analyzed data from the 2016-2017 National Surgical Quality Improvement Program (NSQIP) public use files. Baseline characteristics and perioperative outcomes were compared between drain and no drain cohorts. RESULTS: A total of 11,626 patients were included; 3281 had a drain placed intraoperatively and 8345 did not. Otolaryngologists were 6.98 times more likely to place a drain after thyroidectomy than general surgeons (P < .001), and patients undergoing subtotal or total thyroidectomy were 2.17 times more likely to have a drain placed than if undergoing partial thyroidectomy (P < .001). Drain placement did not reduce hematoma formation on both univariate and multivariate analyses (adjusted OR = 0.93, P = .696). A slightly larger proportion of patients underwent unplanned intubation postoperatively among those who had a drain placed (0.76% vs. 0.29%, P < .001). Patients who received a drain were on average 4.63 times as likely to remain in the hospital for 2 or more days compared to those who did not receive a drain. CONCLUSION: Drain placement did not significantly affect postoperative hematoma formation following thyroidectomy. Drain placement should not be routinely employed in these patients. However, surgeon judgement and intraoperative considerations should be taken into account, as to when to place a drain. LEVEL OF EVIDENCE: N/A Laryngoscope, 130:1349-1356, 2020.


Assuntos
Drenagem , Hematoma/prevenção & controle , Tempo de Internação/estatística & dados numéricos , Complicações Pós-Operatórias/prevenção & controle , Tireoidectomia/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Drenagem/instrumentação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
9.
J Cancer ; 10(27): 6910-6914, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839826

RESUMO

CCL18 is a cytokine secreted by M2 type tumor associated macrophages, which frequently over-expressed in diverse human cancers. However, the clinical significance of serum CCL18 in patients with laryngeal squamous cell carcinoma (LSCC) remains unknown. In this study, serum CCL18 was initially quantified by enzyme-linked immunosorbent assay (ELISA) in 146 patients with LSCC, 25 patients with precancerous lesions and 72 healthy volunteers. In addition, the correlations between serum CCL18 and clinicopathological parameters were analyzed. Our data revealed that serum CCL18 was obviously increased in patients with LSCC. Moreover, serum CCL18 level was significantly associated with primary tumor site (Glottic vs Others), T classification (T1+T2 vs T3+T4), clinical stage (I+II vs III+IV) and lymph node metastasis (N0 vs N+). Survival analysis demonstrated that patients with high serum CCL18 displayed a shorter survival time than those in patients with low serum CCL18. Importantly, serum CCL18 level and clinical stage were independent prognostic factors in patients with LSCC. Taken together, serum CCL18 could be used as a promising biomarker in patients with LSCC.

10.
J Cell Mol Med ; 23(4): 2689-2701, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30768878

RESUMO

Metastasis is one of the primary causes for high mortality in patients with squamous cell carcinoma of the head and neck (SCCHN). Our previous study showed that chemokine (C-C motif) ligand 18 (CCL18), derived from tumour-associated macrophages (TAMs), regulates SCCHN metastasis by promoting epithelial-mesenchymal transition (EMT) and preserving stemness. However, the underlying mechanism needs to be further investigation. Interestingly, metadherin (MTDH) expression was induced when SCCHN cells were stimulated with recombinant CCL18 protein in this study. Suppressing MTDH expression reversed CCL18-induced migration, invasion and EMT in SCCHN cells. Furthermore, the NF-κB signalling pathway was involved in the MTDH knock-down cells with CCL18 stimulation. We performed ELISA to evaluate the CCL18 levels in the serums of 132 treatment-naive SCCHN patients, 25 patients with precancerous lesion and 32 healthy donors. Our results demonstrated that serum CCL18 levels were significantly higher in SCCHN patients than patients with precancerous lesion and healthy individuals. CCL18 levels were found to be significantly correlated with tumour classification, clinical stage, lymph node metastasis and histological grade in SCCHN patients. Thus, our findings suggest that CCL18 may serve as a potential biomarker for diagnosis of SCCHN and promote SCCHN invasion, migration and EMT by MTDH-NF-κB signalling pathway.


Assuntos
Quimiocinas CC/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Proteínas de Membrana/genética , NF-kappa B/genética , Proteínas de Ligação a RNA/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Idoso , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Quimiocinas CC/sangue , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Linfática , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , NF-kappa B/sangue , Estadiamento de Neoplasias , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/antagonistas & inibidores , Proteínas de Ligação a RNA/sangue , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
12.
Sci Rep ; 8(1): 15250, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30323196

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is a common malignant cancer that accounts for 5-10% of all cancers. This study aimed to identify essential genes associated with the prognosis of HNSCC and construct a powerful prognostic model for the risk assessment of HNSCC. RNAseq expression profile data for the patients with HNSCC were obtained from the TCGA database (GEO). A total of 500 samples with full clinical following-up were randomly divided into a training set and a validation set. The training set was used to screen for differentially expressed lncRNAs. Single-factor survival analysis was performed to obtain lncRNAs that associated with prognosis. A robust likelihood-based survival model was constructed to identify the lncRNAs that are essential for the prognosis of HNSCC. A co-expression network between genes and lncRNAs was also constructed to identify lncRNAs co-expressed with genes to serve as the final signature lncRNAs for prognosis. Finally, the prognostic effect of the signature lncRNAs was tested by multi-factor survival analysis and a scoring model for the prognosis of HNSCC was constructed. Moreover, the results of the validation set and the relative expression levels of the signature lncRNAs in the tumour and the adjacent tissue were consistent with the results of the training set. The 5 lncRNAs were distributed among 3 expression modules. Further KEGG pathway enrichment analysis showed that these 3 co-expressed modules participate in different pathways, and many of these pathways are associated with the development and progression of disease. Therefore, we proposed that the 5 validated lncRNAs can be used to predict the prognosis of HNSCC patients and can be applied in postoperative treatment and follow-up.


Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Transcriptoma , Idoso , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Análise de Sobrevida
13.
Cancer Cell Int ; 18: 120, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30181713

RESUMO

Background: Alternatively activated macrophages in tumor microenvironment is defined as M2 tumor-associated macrophages (M2 TAMs) that promote cancer progression. However, communicative mechanisms between M2 TAMs and cancer cells in squamous cell carcinoma of head and neck (SCCHN) remain largely unknown. Methods: Quantitative real-time PCR, western blotting, enzyme-linked immunosorbent assay and flow cytometry were applied to quantify mRNA and protein expression of genes related to M2 TAMs, epithelial-mesenchymal transition (EMT) and stemness. Wounding-healing and Transwell invasion assays were performed to detect the invasion and migration. Sphere formation assay was used to detect the stemness of SCCHN cells. RNA-sequencing and following bioinformatics analysis were used to determine the alterations of transcriptome. Results: THP-1 monocytes were successfully polarized into M2-like TAMs, which was manifested by increased mRNA and protein expression of CCL18, IL-10 and CD206. Conditioned medium from M2-like TAMs promoted the migration and invasion of SCCHN cells, which was accompanied by the occurrence of EMT and enhanced stemness. Importantly, CCL18 neutralizing antibody partially abrogated these effects that caused by conditional medium from M2-like TAMs. In addition, recombinant human CCL18 (rhCCL18) correspondingly promoted the malignant biological behaviors of SCCHN in vitro. Finally, RNA-sequencing analysis identified 331 up-regulated and 363 down-regulated genes stimulated by rhCCL18, which were statistically enriched in 10 cancer associated signaling pathways. Conclusion: These findings indicate that CCL18 derived from M2-like TAMs promotes metastasis via inducing EMT and cancer stemness in SCCHN in vitro.

14.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 43(6): 685-690, 2018 Jun 28.
Artigo em Chinês | MEDLINE | ID: mdl-30110013

RESUMO

Prolin-rich Akt substrate of 40 kD (PRAS40) is firstly identified as a partner of 14-3-3 protein and a substrate of Akt kinase by Roth et al in 2003. Accumulated evidence shows that PRAS40 is mainly activated by phosphorylate modification at different sites. PRAS40 may be involved in various of signaling pathways, such as mammalian target of rapamycin complex 1 (mTORC1), protein kinase B (Akt), NF-κB and ribosomal protein L11 (RPL11) etc, which can regulate cell proliferation, senescence, autophagy, apoptosis and exosome secretion.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo
15.
J Cancer ; 9(1): 198-204, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29290786

RESUMO

Purpose: Lysine demethylase (KDM) 5B, as a member of the histone lysine demethylase family, is overexpressed and functions abnormally in various human cancers. However, its expression in the squamous cell carcinoma of the head and neck (SCCHN) remains unclear. Methods: KDM5B expression was analyzed by immunohistochemistry and correlated with clinicopathological parameters in 103 archival SCCHN tissue samples and 24 adjacent noncancerous epithelial tissues. Results: We found that KDM5B expression was higher in SCCHN than that in adjacent noncancerous tissues. This was closely associated with lymph node metastasis and tumor recurrence. In addition, Kaplan-Meier analysis revealed that patients with high KDM5B expression had shorter disease-free and overall survival times than those with low KDM5B expression. Importantly, both univariate and multivariate analysis demonstrated that KDM5B level was an independent prognostic factor in SCCHN patients. Conclusions: These results indicate that KDM5B is a valuable biomarker that can be used to predict SCCHN patient outcome.

16.
Oncol Rep ; 38(5): 2893-2900, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28901527

RESUMO

Hypoxia is a hallmark of progressive cancer. Hypoxic cancer cells trigger glycolysis in response to a decreased O2 supply to meet metabolic and bioenergetic demands. Meanwhile, these responses to hypoxia and alterations of the microenvironment promote cancer cell metastasis by increasing transcription of hypoxia-inducible factor (HIF)-regulated genes. However, the detailed mechanism by which hypoxia regulates cancer cell metastasis and glycolysis remains to be investigated. In the present study, we identified that metadherin (MTDH), a multifaceted oncogene, is involved in the regulation of head and neck squamous cell carcinoma (HNSCC) metastasis and invasion under hypoxic conditions. Furthermore, the study indicated that there is a positive feedback loop between HIF-1α and MTDH in HNSCC cells, and that hypoxia promotes HNSCC cell metastasis and epithelial-mesenchymal transition by mediating the HIF-1α-MTDH loop. These findings implicate HIF-1α-MTDH as a promising target for anticancer drugs in solid tumors, and help to explain the pro-tumorigenic and unfavorable effect of MTDH on HNSCC observed in our previous studies.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Moléculas de Adesão Celular/metabolismo , Glicólise , Neoplasias de Cabeça e Pescoço/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Movimento Celular , Transição Epitelial-Mesenquimal , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Membrana , Invasividade Neoplásica , Proteínas de Ligação a RNA , Carcinoma de Células Escamosas de Cabeça e Pescoço
17.
J Cancer ; 8(12): 2336-2345, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28819438

RESUMO

Derlin-1 is over-expressed to function as an oncoprotein in breast, lung and colon cancers. However, the implications of Derlin-1 involved in squamous cell carcinoma of the head and neck (SCCHN) remain unknown. This study aims to investigate the effects of Derlin-1 expression on SCCHN tissues and cells. The potential mechanism of Derlin-1 regulating SCCHN cell proliferation, apoptosis and metastasis was also indicated in this work. Western blot and immunohistochemistry (IHC) assays showed that Derlin-1 was over-expressed in 114 SCCHN samples and five SCCHN cell lines. We found that the expression of Derlin-1 was positively associated with lymph node metastasis, clinical stage and recurrence in our SCCHN patients' samples. Survival analysis indicated that high expression of Derlin-1 was significantly associated with shorter overall survival (OS) and disease-free survival (DFS). Knock down expression of Derlin-1 in SCCHN cell lines was found to inhibit cell proliferation, metastasis and promote cell apoptosis. Further experiments showed that signals of PI3K/Akt, p53 and Smad2/3 may involve in these processes. In all, Derlin-1 might be a novel prognostic marker of SCCHN patients and plays an oncogenic role in SCCHN cell progression.

18.
Am J Cancer Res ; 7(12): 2554-2565, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29312808

RESUMO

PURPOSE: MicroRNAs function through regulating specific target mRNA expression and then participate in the development and progression of diverse human cancers. MiR-98 shows aberrant expression and dysfunction in tumors. However, its clinical significance and exact role in squamous cell carcinoma of the head and neck (SCCHN) remain elusive. METHODS: MiR-98 expression was examined by qRT-PCR and correlated with clinicopathological variables and prognosis in SCCHN patients. Effects of miR-98 on epithelial-mesenchymal transition (EMT) and the malignant phenotypes of SCCHN were studied. Finally, the role of target gene metadherin (MTDH) in miR-98 mediated effects were assayed. RESULTS: Our results demonstrated that miR-98, as an endogenous inhibitor of MTDH via directly binding to its 3'-untranslated region (UTR) region, decreased significantly in SCCHN tissues. Decreased miR-98 expression was negatively correlated with T classification, clinical stage, lymph node metastasis and a shorter survival status in SCCHN patients. Loss-of-function and gain-of-function analyses confirmed that miR-98 inhibited cell proliferation, migration and invasion of SCCHN cells in vitro. Moreover, miR-98 repression led to increased MTDH expression and induced EMT alteration. Importantly, ectopic expression of MTDH partially reversed the effects caused by miR-98 overexpression. CONCLUSIONS: Our study identifies that miR-98 serves as a suppressor in SCCHN progression via targeting oncogene MTDH.

19.
Medicine (Baltimore) ; 94(6): e502, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25674742

RESUMO

Our previous study indicated overexpression of metadherin (MTDH) is an adverse prognostic factor in squamous cell carcinoma of the head and neck (SCCHN) and promotes SCCHN cell proliferation and invasion. However, its mechanism remains unclear. Recent studies have indicated that MTDH is a cancer-metastasis-associated molecule that participates in the process of angiogenesis. Therefore, the study is aimed to investigate that whether vascular endothelial growth factor (VEGF), as one of the most potent proangiogenic cytokines, is regulated by MTDH and the role of the phosphatidylinositide 3-kinases/Protein Kinase B (PI3K/Akt) pathway in this process of regulation and the clinical significance of both MTDH and VEGF in SCCHN.Immunohistochemistry was used to assay the expression of MTDH and VEGF in a cohort of 189 SCCHN patients with intact follow-up information. The expression of MTDH was then upregulated or inhibited by lentivirus-mediated MTDH Complementary deoxyribonucleic acid or MTDH short hairpin ribonucleic acid (shRNA) to observe the resulting alterations in VEGF expression and the PI3K/Akt signaling pathway in SCCHN cell lines. In addition, the PI3K/Akt pathway was modulated to observe the resulting changes in the MTDH-mediated expression of VEGF.The immunohistochemistry data showed that MTDH expression is positively correlated with VEGF expression in SCCHN tissues. Moreover, the overexpression of MTDH in SCCHN Tu686 and 5-8F cells led to increases in the expression of VEGF, and this effect was accompanied by activation of the PI3K/Akt pathway. Conversely, shRNA-mediated knockdown of MTDH led to decreased VEGF expression. In addition, inhibition of the Akt signaling pathway reversed the upregulation of VEGF resulting from MTDH overexpression. Moreover, the survival analysis revealed that VEGF is an independent prognostic factor, and a combined survival analysis based on both MTDH and VEGF showed synergistic effects in the prognosis evaluation of SCCHN patients.The findings of the present study demonstrate that MTDH regulates the expression of VEGF via the PI3K/Akt signaling pathway, indicating the potential role of the MTDH-mediated activation of VEGF signaling pathway in SCCHN angiogenesis and metastasis.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Moléculas de Adesão Celular/fisiologia , Neoplasias de Cabeça e Pescoço/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Western Blotting , Carcinoma de Células Escamosas/mortalidade , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Imuno-Histoquímica , Proteínas de Membrana , Prognóstico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , RNA Interferente Pequeno/fisiologia , Proteínas de Ligação a RNA , Transdução de Sinais/fisiologia , Transfecção , Regulação para Cima
20.
Epigenomics ; 7(2): 143-53, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25496457

RESUMO

AIM: Overexpression of histone demethylase PHF8 has been reported to function as an oncoprotein in many cancers; however, the implications of PHF8 involvement in laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remain unclear. This study aims to explore the expression of PHF8 and its clinical significance in LHSCC. MATERIALS & METHODS: Western blotting and immunohistochemistry were performed to evaluate PHF8 protein expression in fresh and archived LHSCC samples. Global expressions of H3K27 and H3K9 methylation were analyzed in a cell line with PHF8 siRNA treatment. RESULTS & CONCLUSION: In our study, PHF8 was upregulated in fresh LHSCC tissues. Immunohistochemical staining revealed that the expression of PHF8 was positively associated with T classification, clinical stage, primary tumor position and tumor relapse. Survival analysis demonstrated that high PHF8 expression was significantly associated with shorter overall survival and disease-free survival. Moreover, PHF8 regulates the levels of H3K9me2 and H3K27me2 in LHSCC. Taken together, PHF8 might be a novel prognostic marker for this disease.


Assuntos
Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/mortalidade , Histona Desmetilases/metabolismo , Neoplasias Hipofaríngeas/enzimologia , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Laríngeas/enzimologia , Neoplasias Laríngeas/mortalidade , Fatores de Transcrição/metabolismo , Linhagem Celular Tumoral , Feminino , Histonas/metabolismo , Humanos , Masculino , Metilação , Prognóstico , Análise de Sobrevida
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