RESUMO
PURPOSE: To determine whether ezrin regulates Yes-associated protein (YAP) and programed cell death ligand-1 (PD-L1), which are involved in the invasion and metastasis of non-small cell lung cancer (NSCLC). METHODS: Immunohistochemistry of 164 NSCLC and 16 para-cancer tissues was performed to detect ezrin, YAP, and PD-L1 expression. Further, H1299 and A549 cells were transfected with lentivirus, and then colony formation, CCK8, transwell, and wound-healing assays were used to assess cell proliferation, migration, and invasion. RT-qPCR and western blotting were used for quantitative analysis of ezrin, PD-L1, and YAP expression. Moreover, the role of ezrin in tumor growth was assessed in vivo, and immunohistochemistry and western blotting were performed to evaluate changes in ezrin expression in mouse samples. RESULTS: The positive protein expression rates of these molecules in NSCLC were as follows: ezrin, 43.9% (72/164); YAP, 54.3% (89/164); and PD-L1, 47.6% (78/164); these were higher than those in normal lung tissues. Moreover, YAP and ezrin expression positively correlated with PD-L1 expression. Ezrin promoted proliferation, migration, invasion, and expression of YAP and PD-L1in NSCLC. Inhibition of ezrin expression reduced the effects of ezrin on cell proliferation, migration, invasion, inhibited the expression of YAP and PD-L1, and obviously reduced experimental tumor volume in vivo. CONCLUSIONS: Ezrin is overexpressed in NSCLC patients and correlates with PD-L1 and YAP expression. Ezrin regulates YAP and PD-L1 expression. Inhibition of ezrin delayed NSCLC progression.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Antígeno B7-H1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão GênicaRESUMO
PURPOSE: c-MYC plays an important role in regulating cellular growth and apoptosis, and it is aberrantly expressed in many human malignancies. Although c-MYC has been extensively investigated in Burkitt lymphoma and diffuse large B cell lymphoma, little has been reported in anaplastic large cell lymphoma (ALCL). The aim of this study was to investigate the expression and genetic alterations of c-MYC in primary systemic ALCL, characterize its clinicopathologic features and immunophenotypes, and discuss their implications in prognosis. METHODS: Tissue microarrays using samples from 85 ALCL patients were used to evaluate expression of c-MYC and anaplastic lymphoma kinase (ALK). c-MYC and ALK genetic alterations were detected using fluorescence in situ hybridization. The Kaplan-Meier and multivariate Cox regression methods were used for survival analysis. RESULTS: c-MYC was expressed in 24 of 85 samples (28.2%), and ALK was expressed in 54 (63.5%). c-MYC and ALK were co-expressed in 16 samples (18.8%). c-MYC expression and c-MYC and ALK co-expression increased with ALCL clinical stages and the International Prognostic Index (IPI) score (p < 0.05). Fifty of the samples (58.8%) had ALK rearrangement, and 18 (22.1%) had aneuploidy. c-MYC rearrangement was not detected, but aneuploidy was observed in 19 cases (22.4%). c-MYC aneuploidy was significantly different based on c-MYC expression and the IPI score (p < 0.05). c-MYC was a significant independent prognostic factor for progression-free survival and overall survival in patients with ALCL. CONCLUSION: c-MYC protein expression and c-MYC aneuploidy could predict worse survival in patients with ALCL.
Assuntos
Quinase do Linfoma Anaplásico/genética , Linfoma Anaplásico de Células Grandes/genética , Linfoma Anaplásico de Células Grandes/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Adolescente , Adulto , Idoso , Quinase do Linfoma Anaplásico/metabolismo , Aneuploidia , Criança , Feminino , Humanos , Hibridização in Situ Fluorescente , Linfoma Anaplásico de Células Grandes/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Proteínas Proto-Oncogênicas c-myc/metabolismo , Análise de Sobrevida , Adulto JovemRESUMO
Objective:To explore the predictive factors for asymptomatic airway hyperresponsivenessï¼AAHRï¼ in patients with chronic rhinosinusitis with nasal polypsï¼CRSwNPï¼. Methods:A total of 76 CRSwNP patients who were hospitalized in the Department of Otorhinolaryngology of Fenyang Hospital affiliated to Shanxi Medical University from May 2016 to October 2020 were retrospectively analyzed, including 40 patients in AAHR group and 36 patients in non-airway hyperresponsivenessï¼non-airway hyperresponsiveness, NAHRï¼ group. The clinical symptoms, CT score of paranasal sinuses, eosinophilï¼EOSï¼ count in peripheral blood and nasal polyp tissue were compared and analyzed. Logistic regression was used to analyze the risk factors of AAHR, and receiver operating characteristics curve was used to judge the predictive value of the parameters. Results:Compared with NAHR group, AAHR group had more symptoms of mouth breathing and postnasal drip, higher total score of CT in ethmoid sinus, sphenoid sinus, olfactory cleft, and more EOS count in peripheral blood and nasal polyp tissue. The differences were statistically significant. There was a positive correlation between EOS count in peripheral blood and in nasal polyp tissueï¼r=0.324, P<0.01ï¼. Postnasal drip, high posterior ethmoid sinusï¼PEï¼ score and nasal polyp tissue EOS count were risk factors for AAHR. The predictive value of nasal polyp tissue EOS count was higher than that of PE scoreï¼AUC=0.786 and 0.685, respectivelyï¼. When the PE score was ≥1.5, the sensitivity was 80.0% and the specificity was 55.6%. When the nasal polyp tissue EOS count was ≥5.67/HPF, the sensitivity was 82.5% and the specificity was 66.7%. Conclusion:The occurrence of AAHR in patients with CRSwNP was related to clinical symptoms, paranasal sinus CT score, peripheral and nasal polyp tissue EOS count. PE score and nasal polyp tissue EOS count can be used to predict AAHR, however nasal polyp tissue EOS has higher predictive value.
Assuntos
Pólipos Nasais , Seios Paranasais , Rinite , Sinusite , Doença Crônica , Eosinófilos , Humanos , Pólipos Nasais/complicações , Estudos Retrospectivos , Rinite/complicações , Sinusite/complicaçõesRESUMO
PURPOSE: To investigate PD-L1 protein expression and gene amplification in lung squamous cell carcinoma (LUSC) and analyse their correlation with the clinicopathological characteristics and prognosis of LUSC patients. PATIENTS AND METHODS: Tissue samples from 164 LUSC patients were collected. PD-L1 protein was detected by immunochemistry (IHC), and PD-L1 gene amplification was investigated by fluorescence in situ hybridization in LUSC patients. RESULTS: The positive expression rate of PD-L1 in LUSC was 47.6% (78/164), and the amplification rate of PD-L1 was 6.7% (11/164); both rates were higher than those of paratumor tissue. Both PD-L1 positive expression and gene amplification were correlated with clinical stage and lymph node metastasis (P<0.05). PD-L1 protein expression, PD-L1 gene amplification, late stage, lymph node metastasis and distant metastasis were significantly correlated with the prognosis of patients. Among these factors, late stage, lymph node metastasis, PD-L1 protein expression and PD-L1 gene amplification were independent prognostic factors for LUSC. CONCLUSION: Positive PD-L1 protein expression and gene amplification are involved in the malignant progression and metastasis of LUSC. Both PD-L1 protein expression and gene amplification are associated with poor prognosis.
RESUMO
Purpose To determine whether ezrin regulates Yes-associated protein (YAP) and programed cell death ligand-1 (PD-L1), which are involved in the invasion and metastasis of non-small cell lung cancer (NSCLC). Methods Immunohistochemistry of 164 NSCLC and 16 para-cancer tissues was performed to detect ezrin, YAP, and PD-L1 expression. Further, H1299 and A549 cells were transfected with lentivirus, and then colony formation, CCK8, transwell, and wound-healing assays were used to assess cell proliferation, migration, and invasion. RT-qPCR and western blotting were used for quantitative analysis of ezrin, PD-L1, and YAP expression. Moreover, the role of ezrin in tumor growth was assessed in vivo, and immunohistochemistry and western blotting were performed to evaluate changes in ezrin expression in mouse samples. Results The positive protein expression rates of these molecules in NSCLC were as follows: ezrin, 43.9% (72/164); YAP, 54.3% (89/164); and PD-L1, 47.6% (78/164); these were higher than those in normal lung tissues. Moreover, YAP and ezrin expression positively correlated with PD-L1 expression. Ezrin promoted proliferation, migration, invasion, and expression of YAP and PD-L1in NSCLC. Inhibition of ezrin expression reduced the effects of ezrin on cell proliferation, migration, invasion, inhibited the expression of YAP and PD-L1, and obviously reduced experimental tumor volume in vivo. Conclusions Ezrin is overexpressed in NSCLC patients and correlates with PD-L1 and YAP expression. Ezrin regulates YAP and PD-L1 expression. Inhibition of ezrin delayed NSCLC progression (AU)