RESUMO
OBJECTIVE: To evaluate the genomic and immune characteristics of non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations from a retrospective dataset with molecular spectrum, tumor mutational burden (TMB), and programmed death-ligand 1 (PD-L1) expression, as well as to evaluate the efficacy of immune checkpoint inhibitors (ICIs). METHODS: A total of 283 patients with EGFR ex20ins mutations who were diagnosed with NSCLC at our hospital from August 2013 to September 2020 were enrolled in this single-center retrospective study. RESULTS: Among the 283 patients with EGFR ex20ins mutations, 182 patients received next-generation sequencing (NGS) test, and 51 different subtypes of insertion variants were recorded. The most common mutations were A767_V769dup (21.4%), S768_D770dup (19.2%) and A763_Y764insFQEA (7.1%). The most common co-occurring mutations were EGFR amplification (37.9%), TP53 mutation (35.0%) and PIK3CA mutation (8.7%). PD-L1 status was available for 141 patients, and 75.9% (107/141) of these samples showed negative PD-L1 expression. In the 36 cases with TMB tested by NGS, the median TMB was 4.6 mutations/Mb. Then 12 patients received ICIs monotherapy or combination therapy. No severe adverse events were observed. CONCLUSION: Low PD-L1 expression and TMB were observed in NSCLC patients harboring EGFR ex20ins mutations. Further investigations are needed to confirm the therapeutic sensitivity of ICIs in this subgroup of EGFR mutations.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Éxons/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Mutagênese Insercional , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Feminino , Regulação da Expressão Gênica , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
This study aims at observing the expression of activated Src tyrosine kinase in esophageal squamous cell carcinoma (ESCC), and exploring the relationship of Src tyrosine kinase with the occurrence and progression of ESCC. Immunohistochemistry, immunofluorescence, and immunoblotting are employed to investigate the expression of Src tyrosine kinase in the ESCC tissue. Cellular immunofluorescence is used to measure the expression of activated Src tyrosine kinase in TE1 and TE9 cell lines of human ESCC tissues and EPC1-htert and EPC2-htert cell lines of esophageal epithelial cells. Src tyrosine kinase is overexpressed in ESCC tissue and underexpressed in normal esophageal mucosa. Furthermore, it is overexpressed in the TE1 and TE9 cell lines of human ESCC tissue and underexpressed in the EPC1-htert and EPC2-htert cell lines of esophageal epithelial cells. Src tyrosine kinase shows a higher expression in human ESCC tissue than in normal esophageal mucosa. The difference is statistically significant (P < 0.05). The activation of Src tyrosine kinase plays an important role in the occurrence and development of ESCC.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , RNA Mensageiro/genética , Quinases da Família src/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Linhagem Celular Tumoral , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Humanos , Plasmídeos/química , Plasmídeos/metabolismo , RNA Mensageiro/metabolismo , Transfecção , Transgenes , Quinases da Família src/metabolismoRESUMO
To understand the beneficial and harmful bio-effects of extremely low frequency electromagnetic fields, we studied the MAPK/ERK signaling pathway based on the Huang-Ferrell model. The sensitivity analysis method was used to study the influence of the model parameters on the activity of ERK, and to further investigate the key biochemical reactions and proteins. The results of the simulation show that an increase in the reaction rate of MAPK/ERK kinase had little effect on ERK activation and the steady-state molecular number. However, a decrease in the reaction rate of MAPK/ERK kinase significantly affected the trigger time of ERK activation and decreased the steady-state molecular number. Together with the biological significance of ERK activity, our findings indicate that the effects of electromagnetic fields are a result of the decrease in the reaction rate of MAPK/ERK kinase, which eventually determines whether these effects cause physical damage or are beneficial in treatment.
Assuntos
Campos Eletromagnéticos/efeitos adversos , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Modelos Teóricos , Animais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , HumanosRESUMO
The critical role of ATP-binding cassette B1 (ABCB1) in the function of the blood-brain barrier led us to conducted this prospective study in order to investigate the clinical outcome of patients suffering from severe traumatic brain injury. A total of 182 patients with traumatic brain injury were included in our study. Genotyping of ABCB1 C3435T and G2677T/A was conducted using polymerase chain reaction-restriction fragment length polymorphism. Using multivariate-logistic regression analysis, we found that patients carrying the CT+CC genotype of ABCB1 C3435T were more likely to have a better neurological outcome when compared with the TT genotype (odds ratio = 2.71, 95% confidence interval = 1.12-6.86). However, no significant association was found between the G2677T/A polymorphism and outcome of traumatic brain injury patients. Our study provides important information regarding the prognostic value of ABCB1 C3435T, and the ABCB1 C3435T polymorphism may be used as a predictive marker for the outcome of traumatic brain injury patients.
Assuntos
Lesões Encefálicas/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/sangue , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Alelos , Barreira Hematoencefálica/metabolismo , Lesões Encefálicas/sangue , Feminino , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Prognóstico , Estudos ProspectivosRESUMO
Mutations in the fibroblast growth factor receptor-3 (FGFR3) gene are frequently found in bladder cancer, but their prognostic value remains controversial. To globally summarize the association between FGFR3 mutations and the grade and stage of bladder cancer, and to analyze the predictive role of FGFR3 mutations with respect to survival, eligible studies were identified and assessed for quality through multiple search strategies. Risk ratio (RR) data were collected from studies comparing the number of FGFR3 mutants among low-grade and early-stage bladder cancer patients to the number among high-grade and late-stage patients. Hazard ratio (HR) data were collected from studies comparing survival in patients with mutant FGFR3 genes to those with wild-type genes. Studies were pooled, and the RRs of grade and stage and the HRs of survival were calculated. Thirty studies were included in the present meta-analysis. FGFR3 mutations were found to be closely associated with low-grade and early-stage bladder cancer, showing pooled RRs = 2.948 [95% confidence interval (CI) = 2.357-3.688] and 2.845 (95%CI = 2.145- 3.773), respectively. Notably, patients with FGFR3 mutations tended to show better disease-, progress-, and recurrence-free survival (HR = 0.561, 95%CI = 0.405-0.779), and better disease-specific survival (HR = 0.363, 95%CI = 0.266-0.496). This study demonstrated that FGFR3 mutations are closely related to low grade, early stage, and better survival among bladder cancer patients.