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1.
Biochem Biophys Res Commun ; 711: 149894, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38603834

RESUMO

BACKGROUND: Low-grade glioma (LGG) has an extremely poor prognosis, and the mechanism leading to malignant development has not been determined. The aim of our study was to clarify the function and mechanism of anoikis and TIMP1 in the malignant progression of LGG. METHODS: We screened 7 anoikis-related genes from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to construct a prognostic-predicting model. The study assessed the clinical prognosis, pathological characteristics, and immune cell infiltration in both high- and low-risk groups. Additionally, the potential modulatory effects of TIMP1 on proliferation, migration, and anoikis in LGG were investigated both in vivo and in vitro. RESULTS: In this study, we identified seven critical genes, namely, PTGS2, CCND1, TIMP1, PDK4, LGALS3, CDKN1A, and CDKN2A. Kaplan‒Meier (K‒M) curves demonstrated a significant correlation between clinical features and overall survival (OS), and single-cell analysis and mutation examination emphasized the heterogeneity and pivotal role of hub gene expression imbalances in LGG development. Immune cell infiltration and microenvironment analysis further elucidated the relationships between key genes and immune cells. In addition, TIMP1 promoted the malignant progression of LGG in both in vitro and in vivo models. CONCLUSIONS: This study confirmed that TIMP1 promoted the malignant progression of LGG by inhibiting anoikis, providing insights into LGG pathogenesis and potential therapeutic targets.


Assuntos
Anoikis , Glioma , Inibidor Tecidual de Metaloproteinase-1 , Humanos , Anoikis/genética , Glioma/genética , Glioma/imunologia , Glioma/patologia , Prognóstico , Inibidor Tecidual de Metaloproteinase-1/genética , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/mortalidade , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Camundongos , Masculino , Proliferação de Células/genética , Feminino , Camundongos Nus , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Gradação de Tumores
2.
Front Genet ; 13: 1024922, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36437961

RESUMO

Background: Extensive research showed costimulatory molecules regulate tumor progression. Nevertheless, a small amount of literature has concentrated on the potential prognostic and therapeutic effects of costimulatory molecules in patients with glioma. Methods: The data were downloaded from The Cancer Genome Atlas (TCGA) database, Chinese Glioma Genome Atlas (CGGA) database, and Gene Expression Omnibus (GEO) database for bioinformatics analysis. R software was applied for statistical analysis. Using the FigureYa and Xiantao online tools (https://www.xiantao.love/) for mapping. Results: The Least absolute shrinkage and selection operator (LASSO) and Cox regression analysis were utilized to identify the signature consisting of five costimulatory molecules. Multivariate regression analysis revealed that the prognosis of glioma could be independently predicted by the riskscore. Furthermore, we explored clinical and genomic feature differences between the two groups. The level of tumor mutational burden (TMB) was higher in the high-risk group, while more mutation of IDH1 was observed in the low-risk group. Results of Tumor Immune Dysfunction and Exclusion (TIDE) analysis showed that high-risk patients were more prone to be responded to immunotherapy. In addition, subclass mapping analysis was performed to validate our findings and the results revealed that a significantly higher percentage of immunotherapy response rate was observed in the high-risk group. Conclusion: A novel signature with a good independent predictive capacity of prognosis was successfully identified. And our findings reveal that patients with high-risk scores were more likely to be responded to immunotherapy.

3.
Artigo em Chinês | MEDLINE | ID: mdl-23858722

RESUMO

OBJECTIVE: To explore the expression of Smac(second mitochondria-derived activator of caspase)and survivin on the growth, development, recurrence and carcinogenesis of the sinonasal inverted papilloma(NIP). METHOD: Immunohistochemical method was used to detective the expression of Smac and survivin in 10 cases of (nasal cavity mucosae, NM), 45 cases of NIP. The NIP group including 25 cases of NIP without dysplasia, 11 cases of NIP with dysplasia, and 9 cases of NIP with malignant transformation to squamous cell carcinoma(SCC). RESULT: The intensity of the positive expression of Smac in NIP was lower than NM, the intensity of the positive expression decreased with the decreasing degree of histological differentiation. There was significantly difference between NIP without dysplasia and SCC. The expression of survivin was negative in the control group, the expression intensity of NIP was enhanced. The degree of histological differentiation was lower, the intensity of the positive expression was higher. The expression between NIP without dysplasia and SCC had significantly differences. Smac negatively correlated with survivin(rs = -0.403, P<0.01). CONCLUSION: Smac and survivin were associated with the growth and carcinogenesis of NIP.


Assuntos
Proteínas Inibidoras de Apoptose/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Mitocondriais/metabolismo , Neoplasias Nasais/metabolismo , Papiloma Invertido/metabolismo , Adulto , Idoso , Proteínas Reguladoras de Apoptose , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Neoplasias Nasais/patologia , Papiloma Invertido/patologia , Survivina
4.
Artigo em Chinês | MEDLINE | ID: mdl-24617005

RESUMO

OBJECTIVE: To investigate the diagnosis of frontal, ethmoid sinus cyst with eye symptoms as initial amount,and the curative effect of nasal endoscopic operation. METHOD: To retrospectively analyze clinical data of sixteen patients with frontal, ethmoid sinus cyst from February 2006 to March 2008. RESULT: Diagnostic accordance rate of paranasal sinus MRI and CT examination In 16 patients is 100%. Fourteen patients' ocular symptoms disappeared after nasal endoscope operation treatment, two of them improved. None of them recurrened after the fol low-up 3-6 years up to now, all the patients had satisfactory curative effect. CONCLUSION: Paranasal sinuses and or bital cavity have close relationship , patients with sinus lesions always firstly visit Ophthalmology doctor. The results of MRI and CT examination are of great value for diagnosis. Patients with frontal, ethmoid sinus cyst with eye symptoms as initial amount should be early diagnosed. The treatment of nasal endoscope operation is safe, effective and is worth of firstly chosen.


Assuntos
Cistos/diagnóstico , Doenças dos Seios Paranasais/diagnóstico , Cistos/cirurgia , Endoscopia/métodos , Osso Etmoide , Seio Etmoidal , Feminino , Seio Frontal , Humanos , Imageamento por Ressonância Magnética , Masculino , Procedimentos Cirúrgicos Nasais , Doenças dos Seios Paranasais/cirurgia , Estudos Retrospectivos
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