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BACKGROUND: HHLA2 (human endogenous retrovirus-H long terminal repeat-associating protein 2) represents a recently identified member of the B7 immune checkpoint family, characterized by limited expression in normal tissues but notable overexpression in various cancer types. Nevertheless, the precise function and interaction with immune cells remain poorly understood, particularly in laryngeal squamous cell carcinoma (LSCC). This investigation endeavored to elucidate the biological significance of HHLA2 within the tumor microenvironment of human LSCC tissues and delineate the clinical relevance and functional roles of HHLA2 in LSCC pathogenesis. METHODS: Through multiplexed immunohistochemistry analyses conducted on tissue microarrays sourced from LSCC patients (n = 72), the analysis was executed to assess the expression levels of HHLA2, density and spatial patterns of CD68+HLA-DR+CD163- (M1 macrophages), CTLA-4+CD4+FoxP3+ (CTLA-4+Treg cells), CTLA-4+CD4+FoxP3- (CTLA-4+Tcon cells), exhausted CD8+T cells, and terminally exhausted CD8+T cells in LSCC tissues. Survival analysis was conducted to evaluate the prognostic significance of HHLA2 and these immune checkpoints or immune cell populations, employing COX regression analysis to identify independent prognostic factors. RESULTS: Kaplan-Meier (K-M) survival curves revealed a significant association between HHLA2 expression and overall survival (OS) in LSCC. Elevated levels of HHLA2 were linked to reduced patient survival, indicating its potential as a prognostic marker (HR: 3.230, 95%CI 0.9205-11.34, P = 0.0067). Notably, increased infiltration of CD68+ cells (total macrophages), STING+CD68+HLA-DR+CD163- (STING+M1 macrophages), CTLA-4+CD4+FoxP3+, CTLA-4+CD4+FoxP3-, PD-1+LAG-3+CD8+T cells, and PD-1+LAG-3+TIM-3+CD8+T cells strongly linked to poorer survival outcomes (P < 0.05). A discernible trend was observed between the levels of these immune cell populations, STING+CD68+ (STING+ total macrophages), CD68+HLA-DR+CD163-, STING+CD68+CD163+HLA-DR- (STING+M2 macrophages), PD-1+LAG-3-CD8+T cells, PD-1+TIM-3+CD8+T cells, and PD-1+LAG-3+TIM-3-CD8+T cells and prognosis. Importantly, multivariate COX analysis identified HHLA2 as an independent predictive factor for OS in LSCC patients (HR = 3.86, 95% CI 1.08-13.80, P = 0.038). This underscored the potential of HHLA2 as a critical marker for predicting patient outcomes in LSCC. CONCLUSIONS: HHLA2 emerged as a detrimental prognostic biomarker for assessing OS in LSCC patients. Relative to other immune checkpoints, HHLA2 exhibited heightened predictive efficacy for the prognosis of LSCC patients.
Assuntos
Biomarcadores Tumorais , Neoplasias Laríngeas , Linfócitos do Interstício Tumoral , Microambiente Tumoral , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Imunoglobulinas , Neoplasias Laríngeas/imunologia , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/patologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Nasopharyngeal carcinoma (NPC) is a malignant tumor with high metastatic features originating from the nasopharynx. However, the underlying mechanism of Suppressor of variegation 3-9 homolog 2 (SUV39H2) in NPC remains poorly understood. RT-qPCR was carried out to examine SUV39H2 and SIRT1 expression in NPC tissues and cells. Kaplan-Meier method was utilized to evaluate the association between SUV39H2 level and overall survival. The function of SUV39H2 and SIRT1 in NPC cell viability, metastasis, and apoptosis was tested through CCK-8, transwell, and flow cytometry experiments. Here, it was uncovered that SUV39H2 level was augmented in NPC tissues and cells. Moreover, SUV39H2 expedited NPC cell viability, metastasis, and inhibited apoptosis, while SIRT1 addition reversed these impacts. Besides, SUV39H2 induced H3K9me3 enhancement to repress SIRT1 transcription via binding to SIRT1 promoter. Collectively, our results demonstrated upregulated SUV39H2 aggravated NPC tumorigenesis through SIRT1, which may offer a potential therapeutic target for NPC.
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The purpose of this experiment was to explore the effects and mechanism of circ_KATNAL1 on inflammatory injury and apoptosis of human middle ear epithelial cells (HMEECs) induced by lipopolysaccharide (LPS). For this aim, the cell inflammatory injury model was established by HMEECs cells induced by LPS. It was divided into a blank control, model, circ_KATNAL1 and circ_KATNAL1 + LPS groups. The cell viability was detected by the MTT method. The apoptosis rate of each group was detected by flow cytometry. The cell migration ability of each group was detected by cell scratch assay. The mRNA expression levels of miR-153-3p and TLR4 in the cells of each group were detected by RT -PCR method. The protein expressions of BCL-2 and TLR4 in the cells of each group were detected by WB method. The levels of IL-6 and TNF-α were detected by ELISA method. Results showed that compared with the control group, the cell viability in the model group was decreased, the cell apoptosis rate was increased, the cell migration ability was weakened, the mRNA expression level of miR-153-3p and protein expression level of BCL-2 in the cells were decreased, and the mRNA and protein expression levels of TLR4 were increased and the levels of IL-6 and TNF-α in the cell supernatant were increased. Compared with the model group, the cell viability in the circ_KATNAL1 group was increased, the cell apoptosis rate was decreased, and the cell migration ability was increased, the mRNA expression level of miR-153-3p and BCL-2 protein expression level in the cells were increased, the mRNA and protein expression levels of TLR4 were decreased, and the contents of IL-6 and TNF-α in the cell supernatant were decreased. Compared with the model group, the cell viability in the circ_KATNAL1 + LPS group was decreased, cell apoptosis rate was increased, cell migration ability was weakened, the mRNA expression level of miR-153-3p and protein expression level of BCL-2 in cells were decreased, mRNA and protein expression levels of TLR4 were increased, and the content of IL-6 and TNF-α in the cell supernatant were increased. The differences were all statistically significant (P ﹤0.05). It showed that LPS could promote cell injury by increasing inflammatory cell pyroptosis, and the abnormal expression of circ_KATNAL1 played an important role in cell inflammation induced by LPS. Up-regulation of circ_KATNAL1 could promote inflammatory pyroptosis in HMEECs induced by LPS. miR-153-5p and TLR4 were downstream targets of circ_KATNAL1. The inhibition of miR- 153-5p or up-regulation of TLR4 could reverse the protective effects of silencing circ_KATNAL1. In conclusion, circ_KATNAL1 can promote an inflammatory role in human middle ear epithelial cells through the miR- 31-5p / TLR4 axis, which may become an important target for the diagnosis and treatment of otitis media.
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Lipopolissacarídeos , MicroRNAs , Humanos , Apoptose/genética , Orelha Média , Células Epiteliais , Inflamação/genética , Interleucina-6/genética , Lipopolissacarídeos/farmacologia , MicroRNAs/genética , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
Nasopharyngeal carcinoma (NPC) is a prevalent tumor in southern China and southeast Asia. Recent studies have demonstrated that viral infection, somatic genetic changes, and epigenetic changes synergistically contribute to NPC pathogenesis. Genome-wide studies show that epigenetic aberrations likely drive nasopharyngeal carcinoma development and progression. This work is aimed at investigating the effect of histone methyltransferase SUV39H2 in NPC. The elevated expression of SUV39H2 in NPC is observed by analyzing GSE53819 and GSE12452 downloaded from the Gene Expression Omnibus (GEO) database. SUV39H2 knockdown inhibits NPC proliferation and induces the apoptosis of cancer cells. At last, RNaseq analysis identifies a variety of SUV39H2 downstream genes related with cancer, in which, NRIP1 is identified as a critical downstream target of SUV39H2 in NPC. Taken together, these findings provide a theoretical basis for understating the biological roles of SUV39H2 in NPC.
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Regulação Neoplásica da Expressão Gênica , Histona-Lisina N-Metiltransferase/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , Proteína 1 de Interação com Receptor Nuclear/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Bases de Dados Genéticas , Progressão da Doença , Epigênese Genética , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Análise de Sequência de RNARESUMO
INTRODUCTION AND IMPORTANCE: Ectopic thyroid carcinoma often occurs in the neck, and metastatic carcinoma of the nasal cavity and sinuses is extremely rare. CASE PRESENTATION: An 11-year-old female was admitted to the hospital for one week due to nasal pain without an obvious cause and blood in the nose. A pale red mass with a peduncle at the back end of the right nasal septum was seen during the operation. Immunohistochemistry showed low-grade papillary thyroid carcinoma. CLINICAL DISCUSSION: Surgeons should be alert to the possibility of ectopic thyroid tissue and related diseases, Patients with suspected malignant lesions should undergo routine pathological examination, and even a normal thyroid should be checked for malignant changes to avoid negative outcomes. CONCLUSION: Although nasal endoscopic surgery is mature, for tumors with unclear properties, it is still necessary to undergo routine pathological examination to avoid habitual errors.
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Objective: The purpose was to evaluate the relationship between peripheral eosinophilia, Japan Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score, and olfactory dysfunction in chronic rhinosinusitis (CRS) patients and to explore the accuracy and specific cut points of the JESREC score in predicting olfactory dysfunction. Methods: In this cross-sectional, retrospective study, olfactory function was assessed by the Sniffin' Sticks 12-item test and multivariate logistic regression analyses were carried out. Receiver operating characteristic curves were plotted to derive accuracy and cutoff values for the JESREC scores of the olfactory dysfunction criterion. Results: A total of 354 patients [mean (SD) age, 50.0 (14.9) years; 41.8% women] were included in the final analysis. The prevalence of olfactory dysfunction was 46.3%. Individuals who had olfactory dysfunction were more likely to be male (64.6% vs. 52.6%), have eosinophilic chronic rhinosinusitis (ECRS) (39.0% vs. 7.9%), have a longer course of CRS (2.3 years vs. 1.5 years), have higher JESREC scores (8.5 vs. 4.5), and have higher proportions of nasal polyps (78.7% vs. 18.9%) and peripheral eosinophilia (3.3% vs. 1.4%). In logistic analysis, the percentage of eosinophils (1.25, 1.13-1.37), JESREC score (1.31, 1.22-1.40), bilateral lesion (2.06, 1.25-3.41), nasal polyps (15.83, 9.23-27.16), CT shadow (2.73, 1.69-4.43), and ECRS (6.86, 3.68-12.80) were associated with olfactory dysfunction in CRS patients after controlling for covariates, while peripheral neutrophils were not significant. In addition, the area under the curve was 0.778 and the cutoff value for JESREC score for olfactory dysfunction was defined as 5.5. Conclusions: Peripheral eosinophilia and high JESREC scores were significantly associated with the risk of olfactory dysfunction in CRS patients, and special attention should be paid to patients with a JESREC score ≥6.
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Eosinofilia , Pólipos Nasais , Transtornos do Olfato , Rinite , Rinossinusite , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Japão/epidemiologia , Estudos Retrospectivos , Pólipos Nasais/patologia , Estudos Transversais , Rinite/complicações , Rinite/epidemiologia , Eosinofilia/patologia , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/complicações , Doença CrônicaRESUMO
Objectives: This study was intended to explore and analyze the factors which affect the survival and prognosis of patients with malignant tumors of nasal cavity and sinus. Methods: Retrospective analysis was performed on the clinical data of 39 cases of malignant tumors of nasal cavity and sinus that met the requirements of the study. A follow-up study was performed on the patients for more than 36 months. Survival analysis was conducted via the Kaplan-Meier method and log-rank test. Cox regression model was used for multivariate analysis. Results: Gender, pathological type, treatment plan, clinical stage, and survival time of patients were different. Clinical stage was substantially related to the survival of patients (P < 0.05), which was an independent factor affecting prognosis. Conclusions: Early detection and comprehensive treatment of sinonasal malignancies can improve the prognosis and prolong the survival time of patients.
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Neoplasias Nasais , Neoplasias dos Seios Paranasais , Seguimentos , Humanos , Neoplasias Nasais/diagnóstico , Neoplasias Nasais/terapia , Neoplasias dos Seios Paranasais/diagnóstico , Neoplasias dos Seios Paranasais/patologia , Neoplasias dos Seios Paranasais/terapia , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Lung cancer is often metastasized to the brain, liver, kidneys, bone, bone marrow, and adrenal glands; however, metastasis of primary lung cancer to the paranasal sinuses is extremely rare. CASE SUMMARY: In this paper, we present a case of metastatic tumors of the sinus secondary to lung adenocarcinoma. The patient was a 46-year-old woman who underwent surgical removal of lung carcinoma. Four months after the surgical removal of the lung tumor, the patient presented with epistaxis, and on investigation, the diagnosis was confirmed to be nasal sinus tumors due to metastasis of lung adenocarcinoma. CONCLUSION: Thorough investigation of patients with epistaxis and a history of lung cancer is necessary to diagnose metastatic sinus tumors. We reviewed relevant literature and found that there are no characteristic clinical or radiologic features for metastatic sinus tumors; however, the diagnosis can be confirmed by histopathological examination of biopsied tumor sample.
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The aim of the present study was to investigate the function of microRNA (miR)-223-5p in the malignant biological behavior of nasopharyngeal carcinoma (NPC) and elucidate the underlying molecular mechanism. The expression levels of miR-223-5p and doublecortin-like kinase 1 (DCLK1) were detected via reverse transcription-quantitative PCR analysis. Cell viability was evaluated using Cell Counting Kit-8 assay. Cell migration and invasion were measured via Transwell assays, while a luciferase reporter assay was conducted to identify the interaction between miR-223-5p and DCLK1. The results demonstrated that miR-223-5p expression was significantly downregulated, whereas DCLK1 expression was significantly upregulated in NPC tissues and cells. Moreover, both miR-223-5p overexpression and DCLK1 silencing markedly suppressed the progression of NPC. It was also observed that miR-223-5p directly targeted DCLK1 and decreased its expression. Furthermore, it was suggested that DCLK1 overexpression may partially reverse the suppressive effects of miR-223-5p on the progression of NPC. Collectively, the results of the present study indicated that miR-223-5p may suppress NPC progression by targeting DCLK1, thereby indicating a novel potential approach to the diagnosis and treatment of NPC.
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Circular RNAs have been reported to play a vital role in the development and progression of various types of cancer. However, the underlying molecular role of circular RNA CTDP1 (circCTDP1) in the tumorigenesis of nasopharyngeal carcinoma (NPC) remains unknown. In the present study, circCTDP1 expression was found to be markedly upregulated in NPC tissues and cell lines (SUNE1, SUNE2 and 610B cell lines). Knockdown of circCTDP1 resulted in inhibition of proliferation, migration and invasion, and promoted apoptosis of NPC cells. Moreover, circCTDP1 directly interacted with microRNA (miR)320b based on bioinformatics prediction and dual luciferase assay, and transfection with an miR320b inhibitor reversed the effects of circCTDP1 knockdown on NPC cells. Furthermore, circCTDP1/miR320b promoted NPC progression by regulating the expression of homeobox A10 (HOXA10). In addition, it was demonstrated that HOXA10 may exert its oncogenic role in NPC by regulating the expression of transforming growth factor ß2 (TGFß2). Taken together, these results revealed a novel regulatory mechanism, which may provide an improved understanding of NPC tumorigenesis and be useful in the development of potential targets for NPC therapy.
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Proteínas Homeobox A10/metabolismo , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/metabolismo , RNA Circular/metabolismo , RNA Longo não Codificante/metabolismo , Fator de Crescimento Transformador beta2/metabolismo , Adulto , Idoso , Animais , Western Blotting , Linhagem Celular , Movimento Celular/genética , Movimento Celular/fisiologia , Biologia Computacional , Progressão da Doença , Feminino , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/genética , Células HEK293 , Proteínas Homeobox A10/genética , Humanos , Técnicas In Vitro , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , RNA Circular/genética , RNA Longo não Codificante/genética , Ratos , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta2/genética , Cicatrização/genética , Cicatrização/fisiologiaRESUMO
Prior studies have shown that apolipoprotein M (APOM) is involved in the development of some cancers. Here we investigated the effects of APOM on larynx cancer (LC). 20 patients with vocal cord polyps and 18 patients with LC were included in this study. The protein and mRNA levels of the samples were analysed using the Wes-ProteinSimple system (or traditional Western blot) and PCR technology, respectively. APOM protein level in cancer tissues was lower than that in paracarcinomatous (P = 0.0003) and polyp tissues (P < 0.0001). APOM overexpression significantly inhibited TU686 cell proliferation (P < 0.0001) and migration (P < 0.01), and increased expression of vitamin D receptor (VDR, P < 0.0001) as well as nuclear factor erythroid 2-like 3 (NFE2L3, P = 0.0215). In addition, matrix metalloproteinase-10 (MMP-10) mRNA level was significantly reduced in the APOM overexpression group (P = 0.0077). However, Western blot analysis showed that APOM overexpression did not change VDR, NFE2L3 and MMP-10 protein levels (P > 0.05). In summary, APOM inhibits the proliferation and migration of LC cells, but may not be related to VDR, NFE2L3 and MMP-10, which needs further study.