RESUMEN
OBJECTIVE: Brain metastases remain lethal in lung cancer patients. The impacts of epidermal growth factor receptor (EGFR) mutations and EGFR tyrosine kinase inhibitors (TKIs) on the incidence of brain metastases in patients with advanced non-squamous non-small cell lung cancer (NSCLC) are still uncertain. PATIENTS AND METHODS: A total of 1672 patients with advanced non-squamous NSCLC with a definitive report on EGFR mutation status between January 2005 and June 2013 were retrospectively analyzed. The impacts of EGFR mutation status and EGFR TKIs use on the incidence of brain metastases and survival were investigated. RESULTS: Of the 1672 patients, 465 (27.8%) had an EGFR mutation, and 1207 (72.2%) did not. Four hundred and eighteen (25.0%) patients had baseline brain metastases. The cumulative incidence of brain metastases for patients in EGFR+ group was significantly higher than patients in EGFR- group (HR, 1.27; 95% CI 1.06-1.52; P=0.008). The cumulative incidence of brain metastases was also higher for patients who received an EGFR-TKI as their first-line treatment than those who received other first-line treatment (HR, 1.36; 95% CI 1.14-1.64; P=0.001). Patients harboring EGFR mutations had prolonged overall survival (OS) than patients with wild-type EGFR (HR, 0.47; 95% CI 0.41-0.54; P<0.001; median, 25.2 vs. 12.9 months). CONCLUSIONS: Both the EGFR mutation-positive status and the use of a TKI are associated with higher incidence of brain metastases for patients with advanced non-squamous NSCLC.
Asunto(s)
Antineoplásicos/efectos adversos , Neoplasias Encefálicas , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB/genética , Neoplasias Pulmonares , Inhibidores de Proteínas Quinasas/efectos adversos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Encefálicas/inducido químicamente , Neoplasias Encefálicas/epidemiología , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/secundario , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Incidencia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mutación , Metástasis de la Neoplasia , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Estudios Retrospectivos , Análisis de Supervivencia , Adulto JovenRESUMEN
The amino acid sequences of beta-tubulin from Toxoplasma gondii stains (GT1 and ME49) and human were aligned by ClustalW2 software. Based on the alignment result, the C-terminal peptides of beta-tubulin of T. gondii were artificially synthesized. Rabbits were immunized with 0.5 mg synthesized peptides for five times at 2-week intervals. Serum samples were collected at the second week after the final immunization, and were analyzed for specific antibodies by ELISA. Finally, the specific-beta-tubulin polyclonal antibody was evaluated by Western blotting with the total protein of RH strain, ME49 strain, and PRU strain of T. gondii, respectively. The results showed that beta-tubulin of T. gondii stains (GT1 and ME49) shared 100% amino-acid sequence identity, and there was 98% amino acid homology between T. gondii and human. The main variable region was the C-terminus. After the fifth immunization, the titers of polyclonal antibody reached 1 : 52,800. Western blotting result indicated that the specific-beta-tubulin polyclonal antibody reacted with beta-tubulin in all the three strains (RH, ME49, and PRU), respectively.
