hsa­miR­455­3P as a predictive biomarker of anemia in patients with non­small cell lung cancer treated with carboplatin plus paclitaxel.

Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. The initial treatment of lung cancer depends on the definition of the tumor type and its staging. The most common treatment is chemotherapy, and the first-line treatment is a combination of carboplatin and paclitaxel. Although this treatment has good efficacy, there is a high prevalence of adverse events, particularly hematological reactions. Studies on new biomarkers related to these adverse events, such as circulating microRNAs (miRNAs/miRs), are important for optimizing the quality of life of patients. miRNAs have high stability in several biological fluids and they have specific expressions in different tissues or pathologies. Thus, the present study aimed to assess the relationship between circulating miRNAs and adverse hematologic reactions caused by treatment with carboplatin + paclitaxel in patients with lung cancer. Blood was collected from patients before and 15 days after chemotherapy for hematological adverse reaction analysis, microarray and quantitative (q)PCR validation. Adverse reactions were classified according to the Common Terminology Criteria for Adverse Events v4.0. Microarray analysis was performed using plasma from six patients without anemia and six patients with anemia, and nine miRNAs were differentially expressed. miR-1273g-3p, miR-3613-5p and miR-455-3p, identified using microarray, were assessed using qPCR in 20 patients without anemia and 26 patients with anemia. Bioinformatic analyses of miR-455-3p were performed using miRWalk, the Database for Annotation, Visualization and Integrated Discovery and GeneMania software. Microarray analysis of patients with and without anemia revealed nine significant differentially-expressed plasma miRNAs among these patients. Of these, miR-1273g-3p, miR-3613-5p and miR-455-3p were chosen for further assessment. Only miR-455-3p demonstrated a significant reduction in expression (P=0.04) between the groups before chemotherapy with carboplatin + paclitaxel. Bioinformatics analysis of miR-455-3p revealed a relationship between this miRNA and the hematopoietic pathway, particularly with respect to the RUNX family transcription factor 1 (RUNX1) and TAL bHLH transcription factor 1, erythroid differentiation factor (TAL1) genes. The most prevalent adverse reactions in patients with lung cancer treated with carboplatin + paclitaxel were hematological, particularly anemia. This adverse reaction, caused by dysfunction of the hematopoietic system, may be explained by a possible association between the important genes in this system, RUNX1 and TAL1, and hsa-miR-455-3p.

Polymorphism of the CYP1A1*2A gene and susceptibility to lung cancer in a Brazilian population.

OBJECTIVE: To estimate and compare the frequency of CYP1A1*2A gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to lung cancer risk. METHODS: The study population included 200 patients with lung cancer, and the control group consisted of 264 blood donors. Genomic DNA was obtained from peripheral blood samples. The PCR-RFLP method was used for analysis of the CYP1A1*2A gene. RESULTS: There was no statistically significant difference between the lung cancer patients and the controls in terms of the distribution of CYP1A1*2A polymorphisms (p = 0.49). A multivariate logistic regression model analysis by ethnic group revealed that, within the lung cancer group, the CYP1A1*2A genotype CC plus TC was more common among the African-Brazilian patients than among the White patients (adjusted OR = 3.19; 95% CI: 1.53-6.65). CONCLUSIONS: The CYP1A1*2A gene cannot be linked with lung cancer risk in Brazilian patients at this time. Larger epidemiologic studies are needed in order to establish whether the CC plus TC polymorphism increases the risk of lung cancer in African-Brazilians.

Polymorphism of the CYP1A1*2A gene and susceptibility to lung cancer in a Brazilian population / O polimorfismo do gene CYP1A1*2A e a suscetibilidade ao câncer de pulmão na população brasileira

OBJECTIVE: To estimate and compare the frequency of CYP1A1*2A gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to lung cancer risk. METHODS: The study population included 200 patients with lung cancer, and the control group consisted of 264 blood donors. Genomic DNA was obtained from peripheral blood samples. The PCR-RFLP method was used for analysis of the CYP1A1*2A gene. RESULTS: There was no statistically significant difference between the lung cancer patients and the controls in terms of the distribution of CYP1A1*2A polymorphisms (p = 0.49). A multivariate logistic regression model analysis by ethnic group revealed that, within the lung cancer group, the CYP1A1*2A genotype CC plus TC was more common among the African-Brazilian patients than among the White patients (adjusted OR = 3.19; 95 percent CI: 1.53-6.65). CONCLUSIONS: The CYP1A1*2A gene cannot be linked with lung cancer risk in Brazilian patients at this time. Larger epidemiologic studies are needed in order to establish whether the CC plus TC polymorphism increases the risk of lung cancer in African-Brazilians.

OBJETIVO: Estimar e comparar a frequência do gene polimórfico CYP1A1*2A na população brasileira e determinar uma possível contribuição dessas variações genéticas no risco para câncer de pulmão. MÉTODOS: A população estudada incluiu 200 pacientes com câncer de pulmão e o grupo controle consistiu em 264 doadores de sangue. O DNA genômico foi obtido de amostras de sangue periférico. O método usado para a análise do gene CYP1A1*2A foi a PCR-RFLP. RESULTADOS: A distribuição do gene CYP1A1*2A polimórfico não foi estatisticamente diferente entre os pacientes com câncer de pulmão e os controles (p = 0,49). Uma análise multivariada utilizando-se o modelo de regressão logística por grupo étnico revelou uma maior frequência do genótipo CC + TC do gene CYP1A1*2A no grupo de pacientes afro-brasileiros do que no grupo de pacientes caucasoides com câncer de pulmão (OR ajustada = 3,19; IC95 por cento: 1,53-6,65). CONCLUSÕES: O gene CYP1A1*2A não pode ser associado ao risco de câncer de pulmão nesta amostra de pacientes. Um extenso estudo epidemiológico é necessário para estabelecer se os genótipos CC + TC aumentam o risco de câncer de pulmão em afro-brasileiros.

Paresia diafragmática bilateral idiopática / Idiopathic bilateral diaphragmatic paresis

Relata-se o caso de um paciente com dispnéia intensa ao se deitar, em que foram excluídas doenças pulmonares, neuromusculares ou cardíacas, cuja investigação revelou paresia diafragmática bilateral. Um sinal chave para o diagnóstico foi a evidência de respiração paradoxal com o doente em decúbito supino. Havia piora da oxigenação e da capacidade vital forçada com a mudança da posição ortostática para supina. A fluoroscopia ortostática foi normal. A pressão inspiratória máxima estava muito reduzida. A estimulação elétrica transcutânea do diafragma foi normal, e a eletroestimulação do nervo frênico mostrou ausência de resposta, permitindo o diagnóstico de paresia bilateral do diafragma.

We report the case of a patient with severe dyspnea upon reclining. Lung disease, neuromuscular disorders and heart disease were ruled out. However, during the course of the investigation, bilateral diaphragmatic paresis was discovered. A key sign leading to the diagnosis was evidence of paradoxical respiration in the dorsal decubitus position. When the patient was moved from the orthostatic position to the dorsal decubitus position, oxygenation and forced vital capacity worsened. The orthostatic fluoroscopy was normal. Maximal inspiratory pressure was severely reduced. The responses to transcutaneous electric stimulation of the diaphragm were normal. However, electric stimulation of the phrenic nerve produced no response, leading to the diagnosis of bilateral diaphragmatic paresis.

Idiopathic bilateral diaphragmatic paresis.

We report the case of a patient with severe dyspnea upon reclining. Lung disease, neuromuscular disorders and heart disease were ruled out. However, during the course of the investigation, bilateral diaphragmatic paresis was discovered. A key sign leading to the diagnosis was evidence of paradoxical respiration in the dorsal decubitus position. When the patient was moved from the orthostatic position to the dorsal decubitus position, oxygenation and forced vital capacity worsened. The orthostatic fluoroscopy was normal. Maximal inspiratory pressure was severely reduced. The responses to transcutaneous electric stimulation of the diaphragm were normal. However, electric stimulation of the phrenic nerve produced no response, leading to the diagnosis of bilateral diaphragmatic paresis.